Accuracy of cuff-less, continuous, and non-invasive blood pressure measurement in 24-h ABPM in children aged 5-17.

PURPOSE: Ambulatory, cuff-less blood pressure (BP) measurement devices are a promising trend to alleviate the strains of conventional, cuff-based BP determination. Cuff-less devices circumvent discomfort and nocturnal arousal reactions which can be triggered by cuff inflation from conventional, cuff-based ambulatory blood pressure measurement devices. Mitigating these discomforts is especially desirable when performing measurement in children. In this study we want to assess the clinical validity of a cuff-less BP measurement device for 24-h measurements in children and adolescents. MATERIALS AND METHODS: We compared the simultaneously retrieved BP data of the cuff-less SOMNOtouch NIBP and the cuff-based Mobil-O-Graph in 24-h use in 90 children in the range from 5 to 17 years old. RESULTS: A total of 1218 valid measurement pairs showed a mean deviation of 0.99 mmHg (limits of agreement: 21.44/-19.46) for systolic and 3.03 mmHg (limits of agreement: 24.37/-18.31) for diastolic BP values. Patient-specific difference of means was within 15 mmHg in 97.7% (systolic BP) and 93.2% (diastolic BP) patients. 25.6% of nocturnal cuff inflations led to determinable, BP-relevant arousal reactions. CONCLUSIONS: The SOMNOtouch NIBP demonstrated little measurement deviation of mean BP compared to the cuff-based technique over a broad spectrum of 24-h, ambulatory BP measurements in children and adolescents. Cuff-less blood pressure measurement relieves the issue of nocturnal arousal reactions which are shown to be frequently induced by cuff-based measurements. Driven by these promising results, we encourage ongoing efforts to create enough evidence on cuff-less BP measurement to promote it into broad clinical application.

What is known about the topic?Hypertension is of increasing relevance in children and adolescentsBlood pressure measurement is difficult, especially in younger individualsWhat this study adds?The study investigated the accuracy of a cuff-less blood pressure (BP) measurement device, SOMNOtouch™ NIBP, in children and adolescents for 24-h measurements, in comparison to a traditional cuff-based device.The experiment involved 90 participants aged between 5 and 17 years old, with both devices worn simultaneously for 24 h.The results indicated that the cuff-less device showed a minor average deviation in BP measurements. The mean deviation for systolic and diastolic BP values was 0.99 mmHg and 3.03 mmHg, respectively.About 25.6% of night-time cuff inflations in traditional devices led to significant arousal reactions.The study concluded that the cuff-less device had a slight measurement deviation and could alleviate issues like nocturnal arousal reactions that are common with cuff-based devices.These findings suggest the potential for broad clinical application of cuff-less BP measurement devices, especially in children and adolescents, to reduce discomfort and improve patient adherence. However, more research is needed to solidify these findings.

Frequency and individual severity of arterial blood pressure changes in children and adolescents with attention-deficit/hyperactivity disorder treated with methylphenidate hydrochloride: a prospective non-interventional study.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common behavioural disorder in childhood. The psychostimulant methylphenidate hydrochloride (MPH) is one of the major pharmacological options for ADHD. MPH is known to result, on average, in a small increase in arterial blood pressure (BP). However, there are few clinical data regarding the individual influences of MPH on BP among children and adolescents with ADHD. According to the European Union-wide standardised patient information sheet for MPH, BP changes >10 mm Hg compared with baseline values are 'common' (ie, ≥1% to <10%) in children and adolescents with ADHD during MPH therapy. AIM: To investigate the frequency and individual severity of BP changes in children and adolescents with ADHD during the first 6 months of new MPH therapy. METHODS: In this study, 44 (77% male) children and adolescents (mean age (SD) 9.13 (1.86) years) with a diagnosis of ADHD according to the International Classification of Diseases, tenth revision, underwent ambulatory BP monitoring before and during the first 6 months of routine MPH therapy. Exclusion criteria were pre-existing MPH therapy and other medications that potentially influence BP or interfere with MPH. The non-interventional study was conducted prospectively at 10 paediatric cardiology centres in Germany and Austria. RESULTS: After beginning MPH therapy, 34% of participants (99% CI 15.52% to 52.66%) had BP increases/decreases >10 mm Hg. The mean changes in systolic BP and diastolic BP were 0.87 mm Hg (95% CI -1.75 mm Hg to 3.48 mm Hg) and 1.96 mm Hg (95% CI 0.21 mm Hg to 3.7 mm Hg), respectively. The proportion of participants with initial prehypertension/hypertension was 54.55%. CONCLUSIONS: In our sample with a high baseline rate of prehypertension/hypertension, BP changes >10 mm Hg during MPH therapy were more frequent than those indicated by the patient information sheet. Moreover, individual BP changes, including increases and decreases >10 mm Hg, resulted in a small average BP increase in the sample, thus reflecting neither the severity nor the direction of individual BP changes. Therefore, the frequency and, due to the common use of the arithmetic mean, the individual severity of BP changes during MPH therapy may be underestimated. Further studies without averaging and with larger samples including patients in primary care settings are warranted.

Increased nocturnal heart rate and wave reflection are early markers of cardiovascular disease in Williams-Beuren syndrome children.

OBJECTIVE: Williams-Beuren syndrome (WBS) is a genetic disorder that involves elastin gene causing cardiovascular abnormalities and increased risk. However, data on arterial function in these patients are only few and conflicting. Aim of this study was to evaluate dynamic behaviour of central and peripheral blood pressure (BP) and arterial stiffness parameters early in the course of WBS. METHODS: We enrolled 19 WBS paediatric patients (age 13 ±â€Š4 years) and 23 age, height and BP-matched controls (10 ±â€Š4 years). We evaluated 24-h ambulatory BP values via an ambulatory blood pressure monitoring (ABPM) system (Mobil-O-Graph) also capable to calculate 24-h central BP and 24-h arterial stiffness parameters. Carotid-femoral PWV (cf-PWV) was assessed in all WBS individuals (Complior). RESULTS: BP values were similar in WBS and control, during the daytime and the night-time. The same behaviour applies to 24-h central BP. However, during the night, WBS showed heart rate values (HR; 78 ±â€Š10 vs. 71 ±â€Š9 bpm; P < 0.03), augmentation index (Aix; 24.6 ±â€Š13.5% vs. 16.5 ±â€Š8.9%; P = 0.03) and reflection magnitude (68 5.8 vs. 63.5 8.1; P = 0.02) higher than controls. The HR, Aix and reflection magnitude reduction in the day-night shift was lower in WBS than in controls. Cf-PWV in WBS children did not differ when compared with their normalized expected value. CONCLUSION: In WBS children, the higher night-time HR, Aix and reflection magnitude and their impaired physiological reduction in the day-night shift suggests an abnormal sympathetic cardiovascular control, an augmented wave reflection and an increase in small arteries resistance. These alterations possibly due to a sympathetic overactivity can be regarded as earlier hallmarks of cardiovascular dysfunction in these patients.

Percentiles for central blood pressure and pulse wave velocity in children and adolescents recorded with an oscillometric device.

OBJECTIVE: In adults with arterial hypertension, measuring arterial stiffness by pulse wave velocity (PWV) can determine the extent of cardiovascular subclinical organ damage. PWV has independent predictive value for cardiovascular events, but there are currently no recommendations for measuring PWV in children. In addition, central systolic blood pressure (cSBP) strongly reflects vascular changes. The aim of this study was to establish percentiles for cSBP and PWV in children and adolescents to evaluate and classify altered vascular function in youths. METHODS AND RESULTS: We measured PWV and cSBP with an oscillometric device with inbuilt ARCSolver-algorithm (estimated by using the brachial waveform) and calculated smoothed reference percentiles for 1445 children and young adults (49.5% female; 13.41 ± 2.80 years, range 8-22 years; PWV 4.67 ± 0.34 m/s; cSBP 100.7 ± 8.9 mmHg) using the LMS-method based on age and height. PWV and cSBP increased with age and height, but slightly differently for girls and boys, possibly reflecting different growth patterns. Between 8 and 21 years, PWV increased from 4.29 ± 0.32 to 4.98 ± 0.33 m/s in girls and from 4.27 ± 0.18 to 5.22 ± 0.46 m/s in boys. While girls showed a minor increase in cSBP (91.2 ± 7.5 to 109.1 ± 8.6 mmHg), the cSBP in boys ranged from 90.0 ± 5.8 to 110.5 ± 9.6 mmHg with a more pronounced increase between 14 and 17 years. CONCLUSION: These percentiles for PWV and cSBP can help define arterial stiffness in youths and contribute to risk stratification for cardiovascular disease. For example, in children with prehypertension or isolated systolic hypertension, PWV and cSBP can provide additional information about the function of the vascular system, thereby strengthening intervention strategies.

Differences in the prevalence of metabolic disorders between prepubertal boys and girls from 5 to 8 years of age.

AIM: To determine the prevalence of metabolic abnormalities, and differences between the sexes, in prepubertal overweight and normal weight children aged from 5 to 8 years, without any signs of health impairments or metabolic disturbances at the time of recruitment. METHODS: General health status and inflammatory markers were assessed in 100 overweight and 51 normal weight children, who were living in Germany and had undergone mandatory medical examinations. The study comprised of 81 girls and 70 boys. RESULTS: Despite being recruited as healthy, 73% of the overweight children and 16% of the normal weight children were found to suffer from one or more metabolic abnormalities, such as hypertension or insulin resistance. Girls with a body mass index (BMI) percentile of ≥80th showed an increased susceptibility to metabolic disorders, and a similar effect was found for boys with a BMI percentile of ≥95th. Plasma levels of proinflammatory markers, such as plasminogen activator inhibitor-1 and leptin, were also significantly higher in overweight than normal weight children. CONCLUSION: Metabolic and cardiovascular abnormalities and pro-inflammatory markers were prevalent in overweight prepubertal children. The prevalence rates appeared to differ between the sexes.

Association of elevated blood pressure with low distress and good quality of life: results from the nationwide representative German Health Interview and Examination Survey for Children and Adolescents.

OBJECTIVE: Quality of life is often impaired in patients with known hypertension, but it is less or not at all reduced in people unaware of their elevated blood pressure. Some studies have even shown less self-rated distress in adults with elevated blood pressure. In this substudy of the nationwide German Health Interview and Examination Survey for Children and Adolescents (KIGGS), we addressed the question whether, also in adolescents, hypertensive blood pressure is linked to levels of distress and quality of life. METHODS: Study participants aged 11 to 17 years (N = 7688) received standardized measurements of blood pressure, quality of life (using the Children's Quality of Life Questionnaire), and distress (Strengths and Difficulties Questionnaire). RESULTS: Elevated blood pressure was twice as frequent as expected, with 10.7% (n = 825) above published age-, sex- and height-adjusted 95th percentiles. Hypertensive participants were more likely to be obese and to report on adverse health behaviors, but they showed better academic success than did normotensive participants. Elevated blood pressure was significantly and positively associated with higher self- and parent-rated quality of life (for both, p ≤ .006), less hyperactivity (for both, p < .005), and lower parent-rated emotional (p < .001), conduct (p = .021), and overall problems (p = .001). Multiple regression analyses confirmed these findings. CONCLUSIONS: Our observation linking elevated blood pressure to better well-being and low distress can partly be explained by the absence of confounding physical comorbidity and the unawareness of being hypertensive. It also corresponds to earlier research suggesting a bidirectional relationship with repressed emotions leading to elevated blood pressure and, furthermore, elevated blood pressure serving as a potential stress buffer.

Oscillometric carotid to femoral pulse wave velocity estimated with the Vicorder device.

Carotid to femoral pulse wave velocity (PWV) is associated with an increase in cardiovascular morbidity and all-cause mortality. Noninvasive approach has made this method applicable for the examination of larger populations. This study aimed to obtain reference values of PWV measured with the Vicorder device. PWV was obtained using the oscillometric Vicorder in 318 healthy, normotensive patients (165 women, 28.7±17.6 years, range 6-83 years). A plethysmographic sensor was placed over the right carotid region to pick up the carotid pulse wave and a blood pressure cuff was placed around the upper thigh to trace the femoral pulse wave. Path length was defined as the distance from the suprasternal notch to the top of the thigh cuff. Mean PWV was 6.1±1.4 m/s and significantly increased with age (r=.842; P<.0001). PWV was associated with mean arterial pressure (r=.546; P<.0001) and body mass index (r=.396; P<.0001). In a multiple linear regression model, age, mean arterial pressure, and body height emerged as independent markers for PWV. This study established reference values for carotid to femoral PWV derived by oscillometric measures that can now be used for risk stratification.

Cardiovascular considerations of attention deficit hyperactivity disorder medications: a report of the European Network on Hyperactivity Disorders work group, European Attention Deficit Hyperactivity Disorder Guidelines Group on attention deficit hyperactivity disorder drug safety meeting.

Regulatory decisions regarding attention deficit hyperactivity disorder drug licensing and labelling, along with recent statements from professional associations, raise questions of practice regarding the evaluation and treatment of patients with attention deficit hyperactivity disorder. To address these issues for the European community, the European Network for Hyperkinetic Disorders, through its European Attention Deficit Hyperactivity Disorder Guidelines Group, organised a meeting between attention deficit hyperactivity disorder specialists, paediatric cardiovascular specialists, and representatives of the major market authorisation holders for attention deficit hyperactivity disorder medications. This manuscript represents their consensus on cardiovascular aspects of attention deficit hyperactivity disorder medications. Although sudden death has been identified in multiple young individuals on attention deficit hyperactivity disorder medication causing regulatory concern, when analysed for exposure using currently available data, sudden death does not appear to exceed that of the general population. There is no current evidence to suggest an incremental benefit to electrocardiography assessment of the general attention deficit hyperactivity disorder patient. Congenital heart disease patients have an increased prevalence of attention deficit hyperactivity disorder, and can benefit from attention deficit hyperactivity disorder therapies, including medication. The attention deficit hyperactivity disorder specialist is the appropriate individual to evaluate benefit and risk and recommend therapy in all patients, although discussion with a heart specialist is reasonable for congenital heart disease patients. For attention deficit hyperactivity disorder patients with suspected heart disease or risk factor/s for sudden death, assessment by a heart specialist is recommended, as would also be the case for a non-attention deficit hyperactivity disorder patient. The identification of risk factors for sudden death should not automatically exclude the use of attention deficit hyperactivity disorder medication.

Beta-blockers for congestive heart failure in children.

BACKGROUND: Beta-blockers are an essential part of standard therapy in adult congestive heart failure and are therefore also expected to be beneficial in children. However, congestive heart failure in children differs strongly from that in adults in terms of characteristics and aetiology; also, an increased drug clearance has been reported. Paediatric needs have therefore to be specifically investigated. OBJECTIVES: To assess the effect of beta-adrenoceptor-blockers in children with congestive heart failure. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 4 2007), MEDLINE (1966 to January 2008), EMBASE (1980 to January 2008), and LILACS (1980 to January 2008). Bibliographies of identified studies were checked. No language restrictions were applied. SELECTION CRITERIA: Randomised, controlled clinical trials investigating the effect of beta-blocker therapy on paediatric congestive heart failure. DATA COLLECTION AND ANALYSIS: Two authors independently extracted and assessed data from the included trials. MAIN RESULTS: Three studies with an overall number of 203 participants were identified. Two small studies, with 20 and 22 children respectively, showed an improvement of congestive heart failure, while a larger study with 161 participants showed no evidence of benefit over placebo in the composite measure of heart failure outcomes which was the main outcome measure of the trial (56% improvement in both the placebo and the treatment group, p=0.74). However, study populations showed vast differences with regard to treatment (choice of beta-blocker, dosing, duration of treatment), age and age range of the participants and in particular with regard to condition (aetiology and severity of heart failure; homogeneity of condition in the study population). In addition methods and outcome measures differed strongly and were not standardised. The results can therefore not be compared against each other. AUTHORS' CONCLUSIONS: There are not enough data to recommend or discourage the use of beta-blockers in children with congestive heart failure. Further investigations in clearly defined populations with standardised methodology are required to establish guidelines for therapy. Pharmacokinetic investigations of beta-blockers in children are required to provide effective dosing in future trials.

Development of a safe and effective pediatric dosing regimen for sotalol based on population pharmacokinetics and pharmacodynamics in children with supraventricular tachycardia.

OBJECTIVES: The objective of this study was to develop age-specific dosage guidelines for sotalol in children with supraventricular tachycardia (SVT) based on a population pharmacokinetic covariate analysis, clinical trial simulations, and pharmacodynamics. BACKGROUND: A rapid onset of an effective and safe antiarrhythmic sotalol therapy, especially for infants and neonates, is frequently delayed because of age-dependent interpatient variability in pharmacokinetics and pharmacodynamics. METHODS: Pediatric patients with SVT (mean age 3.51 years [range 0.03 to 17 years]) were analyzed after oral sotalol doses of 1.0 to 9.9 mg/kg/day using population pharmacokinetic analysis and clinical trial simulation (n = 76), pharmacokinetic/pharmacodynamic modeling for QT interval prolongation (n = 32), and for the concentration-antiarrhythmic-response relationship (n = 15). RESULTS: Inter-individual differences in oral clearance and volume of distribution could largely be attributed to size and weight differences, with an additional age effect on clearance in children younger than one year. Neonates showed a higher sensitivity toward QTc interval prolongation compared with older patients. In a subgroup of 15 patients, one-half of the patients converted into sinus rhythm at sotalol trough levels of 0.4 mug/ml and more than 95% at 1.0 mug/ml. Dosing recommendations derived for different age groups based on these findings were starting dose and target dose of 2 and 4 mg/kg/day for neonates, 3 and 6 mg/kg/day for infants and children <6 years, and 2 and 4 mg/kg/day for children >6 years. CONCLUSIONS: This study provides an example for rational drug dosage in children that copes with interpatient variability and can be easily switched to an individually guided therapy based on effective sotalol trough levels.

Effects of therapeutic beta blockade on myocardial function and cardiac remodelling in congenital cardiac disease.

BACKGROUND: Cardiac remodelling is now recognised as an important aspect of cardiovascular disease progression and is, therefore, emerging as a therapeutic target in cardiac failure due to different etiologies. Little is known about the influence of different therapies for cardiac failure on the remodelling seen in infants with congenital cardiac disease. METHODS: During follow-up of a prospective and randomized trial, we investigated therapeutic effects on neurohormonal activation, ventricular function, and myocardial gene expression. We compared the data from 8 infants with severe congestive heart failure due to left-to-right shunts, who received digoxin and diuretics alone, to 9 infants who received additional treatment with propranolol. RESULTS: In these infants, beta-adrenergic blockade significantly reduced highly elevated levels of renin, from 284 +/- 319 microU/ml compared to 1061 +/- 769 microU/ml. Systolic ventricular function was normal in both groups, but diastolic ventricular function was improved in those receiving propranolol, indicated by significantly lower left atrial pressures, lower end-diastolic pressures, and less pronounced ventricular hypertrophy, the latter estimated by lower ratios of myocardial wall to ventricular cavity areas on average of 42%. Further hemodynamic parameters showed no significant differences between the groups, except for the lower heart rate in infants treated with propranolol. In those treated with digoxin and diuretics, there was a significant downregulation of beta2-receptor and angiotensin-2 receptor genes, and up-regulation of endothelin A receptor and connective tissue growth factor genes, that were partially prevented by additional treatment with propranolol. CONCLUSIONS: Beta-blockade is a new therapeutic approach for congestive heart failure in infants with congenital cardiac disease, producing with significant benefits on neurohormonal activation, diastolic ventricular function, and cardiac remodelling.

Heart rate variability in infants with heart failure due to congenital heart disease: reversal of depressed heart rate variability by propranolol.

BACKGROUND: Analysis of heart rate variability (HRV) provides a noninvasive index of autonomic nervous system activity. HRV has shown to be reduced in congestive heart failure and in children with congenital heart disease (CHD). Beta-blockers improve HRV in adults with congestive heart failure, but this improvement remains to be demonstrated in children. MATERIAL/METHODS: HRV was analysed in 14 infants with severe heart failure due to CHD who received a 'standard' therapy with digoxin and diuretics ('Digoxin/Diuretics' group) and in 9 of these patients with an additional propranolol therapy ('Propranolol' group) 17 days later on average and compared with HRV of 70 healthy infants ('Healthy Control'). RESULTS: Comparing the 'Digoxin/Diuretics' group versus 'Healthy Control', we found significantly reduced HRV in the time domain and the frequency domain, that could be abolished in the 'Propranolol' group. None of the HRV parameter were significantly related to age or any hemodynamic parameter but inversely related to ejection fractions within the normal range (pNN50: r= -0.58, p=0.004; rMSSD: r= -0.42; p=0.049). HRV measurements (SDNN, r= -0.48) and plasma norepinephrine levels (r=0.7) were significantly related to clinical symptoms of heart failure, measured by the Ross Score. CONCLUSIONS: HRV represents a noninvasive parameter that is reduced in infants with congenital heart disease depending on the severity of heart failure but not on hemodynamic disturbances. Propranolol but not digoxin therapy effectively reduced the supposed autonomic imbalance in infants with severe heart failure due to CHD.

BMS-193884 and BMS-207940 Bristol-Myers Squibb.

Bristol-Myers Squibb is developing BMS-193884, an oral endothelin antagonist, for the potential treatment of congestive heart failure (CHF) and pulmonary hypertension [206604]. The compound entered phase I trials in November 1996 [242721] and had progressed to phase II trials [399460], [441398]. Structural modifications led to the development of a second-generation analog, BMS-207940, a biphenylsulfonamide endothelin A receptor-selective antagonist, and the probable discontinuation of the first clinical candidate, BMS-193884 [446511]. By April 2002, BMS-207940 was in phase I trials [446511]. By March 2002, filing for NDA was expected to take place in 2004 at the earliest [452734].

Beta-receptor downregulation in congenital heart disease: a risk factor for complications after surgical repair?

BACKGROUND: Neurohormonal activation in children with heart failure due to congenital heart disease leads to downregulation of myocardial beta-receptors that may influence the postoperative course after cardiothoracic surgery. METHODS: Myocardial biopsies of 26 children (aged 14+/-4 months) were obtained from the right atrium during cardiac surgery. Patients were allocated to either of two groups based on the duration of their intensive care unit stay: group 1 comprised those who stayed less than 7 days (n = 17), whereas group 2 comprised those who stayed more than 7 days, plus 3 infants who died during the early postoperative course (n = 9). For beta1- and beta2-mRNA quantitation, real-time polymerase chain reaction with fluorescence-labeled products was used. RESULTS: Values for myocardial beta1-receptor gene expression were twice as high in group 1 children compared with group 2 (beta1-receptor 0.12+/-0.07 versus 0.06+/-0.03, p = 0.0016; beta2-receptor 0.12+/-0.07 versus 0.06+/-0.03, p = 0.0071). Beta-receptor gene expression in 16 children who received standard treatment for heart failure averaged lower than in the 10 children who received additional propranolol. CONCLUSIONS: Beta-receptor downregulation due to congestive heart failure has an impact on the postoperative course in children with congenital disease and depends on heart failure therapy.