Peak Circulatory Power as an Indicator of Clinical Status in Children After Fontan Procedure

Peak circulatory power (CircP), a product of peak exercise oxygen uptake (VO₂) and peak mean or systolic arterial blood pressure, has proved to be a strong predictor of poor outcome in adults with congenital heart disease. This study sought to compare CircP with other cardiopulmonary exercise (CPX) test variables and to assess whether CircP is superior in categorizing patients into well-functioning vs. poorly functioning at-risk groups in the pediatric population after a Fontan procedure. The CPX test reports of 50 patients were retrospectively reviewed after the Fontan procedure. The patients were divided into two groups. The well-functioning group included patients in New York Heart Association (NYHA) classes 1 and 2 (n = 36). The poorly functioning at-risk group included patients in NYHA classes 3 and 4 and those with significant indicators or outcomes of a poor prognosis (n = 14). The patients in the well-functioning group had significantly higher CircP values based on mean blood pressure (MBP) (P < 0.001), higher CircP values based on systolic blood pressure (SBP) (P < 0.001), and higher peak VO₂ (P = 0.004) than those in the poorly functioning at-risk group. At a cutoff value less than 2100.4 mmHg/mlO₂/kg/min, CircP MBP had a sensitivity of 85% in categorizing children to the poorly functioning at-risk group. CircP correlated well with the clinical status of our patients. CircP and peak VO₂ did not differ significantly in ability to identify poorly functioning patients. Further prospective analysis is needed to assess whether CircP can serve as a prognostic marker for the pediatric population after Fontan procedure.     

Diastolic Function and Patient-Reported Quality of Life for Adolescents and Adults With Repaired Tetralogy of Fallot: A Tissue Doppler Study

Left ventricular systolic function is an important indicator of clinical well-being and outcomes for patients with repaired tetralogy of Fallot (TOF). This study tested the hypothesis that left ventricular diastolic function by pulsed-wave tissue Doppler is associated with quality of life in this population. In this study, 38 subjects (age, 31.0 ± 14.1 years) with repaired TOF underwent echocardiogram and completed the Short-Form 36, version 2, a validated quality-of-life assessment, within a median of 0 days (range, 0–90 days). Available cardiovascular magnetic resonance data within 1 year after the echocardiogram were analyzed. The ratio of peak early inflow to peak early annular velocity (E/E′) at the lateral mitral annulus correlated inversely with the ability to participate in usual activities without physical limitations (r = −0.37; p = 0.02), whereas the right ventricular diastolic indices were not predictive. The relation of left ventricular diastolic function to quality of life was independent of left ventricular systolic function. This may be related to adverse ventricular–ventricular interactions because lateral mitral E/E′ correlated with tricuspid E/E′ (r = 0.46; p = 0.008) and the right ventricular myocardial performance index (r = 0.42; p = 0.01). Pulsed-wave tissue Doppler of the mitral annulus is a useful tool in this population and may potentially identify patients in need of intervention before the development of left or right ventricular systolic dysfunction.     

Assessment of Coronary Flow Reserve in the Coronary Sinus by Cine 3T-Magnetic Resonance Imaging in Young Adults after Surgery for Tetralogy of Fallot

This study aimed to evaluate CFR by assessing blood flow in the coronary sinus and systemic endothelial function measured by FMD of the brachial artery in an open prospective study of 10 control subjects and 10 patients (ages, 15–25 years) who have undergone surgical TOF repair. Reduced ventricular function, impaired exercise capacity, and ventricular arrhythmia have been proposed as risk factors for sudden cardiac death after surgical repair of TOF. Some of this may be related to impaired myocardial perfusion. A 3.0T GE Signa Excite scanner was used to achieve phase-contrast, velocity-encoding cine magnetic resonance imaging in the coronary sinus before and during infusion with adenosine (0.14 mg/kg/min). FMD was measured in the brachial artery before arterial occlusion and 5 min afterward. The TOF group demonstrated significantly higher volumetric blood flow in the coronary sinus (282 ± 63 ml/min) than the normal control subjects at rest (184 ± 57 ml/min) (P = 0.006). During adenosine infusion, this difference disappeared. The CFR was 2.00 ± 0.43 in the control group and 1.19 ± 0.34 in the TOF group (P = 0.002). No correlation between FMD and CFR was observed in the study group (r _s = 0.61, n = 8, P = 0.15). This study showed a reduced CFR due to a higher blood flow of the subject at rest in the TOF group. This reduced CFR may disable a normal adaptation to increased oxygen demand during exercise and increase myocardial vulnerability to reduced blood supply postoperatively for TOF patients with coronary heart disease.     

Responses of Plasma Norepinephrine and Heart Rate During Exercise in Patients After Fontan Operation and Patients with Residual Right Ventricular Outflow Tract Obstruction After Definitive Reconstruction

To determine the exercise responses of patients with congenital heart disease, 20 patients—5 who had undergone a right ventricular outflow tract reconstruction (group R; age, 15 ± 2 years), eight who had undergone a Fontan operation (group F; age, 13 ± 2 years), and seven who had a history of Kawasaki disease (group C; age, 15 ± 1 years)—performed a treadmill exercise test. Patients of group R had a significant residual right ventricular outflow obstruction. Oxygen uptake (VO₂), heart rate (HR), and plasma norepinephrine (NE) concentrations were measured at rest, during warm-up, at ventilatory threshold (VT), and at peak exercise. Exercise capacity was determined as a percentage of the predicted normal peak VO₂ (%pVO₂). The %pVO₂ for groups R and F was 65 ± 10 and 56 ± 11, respectively. Peak HR for groups R and F was 171 ± 4 and 155 ± 5, which were lower than the HR for group C (p < 0.001). Although NE concentrations at rest, during warm-up, and at VT were significantly greater in groups R and F (p < 0.05), there were no significant differences in the NE concentrations at peak exercise. Peak HR correlated with %pVO₂ (p < 0.001). The ratio of the increase in HR to NE from rest to VT was significantly lower in groups R and F than in group C (p < 0.001) and correlated with %pVO₂ (r= 0.80; p < 0.001). These data suggest that sympathetic nervous activity in groups R and F is increased at rest and during mild to moderate exercises, and reduced sinus node sensitivity to NE may be partly responsible for the abnormal HR response during exercise of patients with uncorrected congenital heart disease.     

Pulmonary Limitation to Exercise After Repair of D-Transposition of the Great Vessels: Atrial Baffle Versus Arterial Switch

This study evaluated resting pulmonary function and its impact on exercise capacity after atrial baffle (BAFFLE) and arterial switch (SWITCH) repair of D-transposition of the great vessels (DTGV). Previously decreased exercise capacity in DTGV patients has been primarily attributed to cardiovascular limitations, whereas pulmonary limitations have largely been overlooked. Resting flow volume loops were compared for BAFFLE (n = 34) and SWITCH (n = 32) patients. Peak exercise variables were compared for BAFFLE (n = 30) and SWITCH (n = 25). Lung disease (restrictive and/or obstructive) was present in 53% of DTGV patients (BAFFLE 62% and SWITCH 44%; p = 0.14). BAFFLE patients had a normal breathing reserve, whereas that of SWITCH patients was decreased (27.3 ± 28.3 vs. 13.0 ± 19.2; p = 0.04). BAFFLE patients attained a lower percent of predicted peak oxygen pulse (82.7 ± 20.5% vs. 94.7 ± 19.3%; p = 0.04) and peak oxygen consumption (VO_2peak) (26.6 ± 6.7 ml/kg/min vs. 37.3 ± 8.5 ml/kg/min; p < 0.01) than SWITCH patients. Patients after surgical repair for DTGV have an underappreciated occurrence of lung disease, even post-SWITCH. SWITCH patients have diminished breathing reserves, suggesting a pulmonary limitation to VO_2peak. BAFFLE patients have lower VO_2peaks, greater breathing reserves, and lower oxygen pulses than SWITCH patients, suggesting a cardiac limitation to peak aerobic capacity with probable secondary pulmonary limitations. Treating underlying lung disease in symptomatic patients after repair of DTGV may improve functional status.     

Myocardial Perfusion and Exercise Capacity 12?Years After Arterial Switch Surgery for D-Transposition of the Great Arteries

Peak exercise myocardial perfusion was evaluated in patients with D-transposition of the great arteries 12 years after the arterial switch operation (SWITCH) to evaluate coronary perfusion. Gas-exchange measurements were used to assess cardiac limiting factors to exercise capacity in SWITCH patients when compared to healthy gender-matched controls (CON). Peak myocardial perfusion was evaluated in 42 patients 12 years post-SWITCH, using technetium-99 m (Tetrofosmin). SWITCH exercise data was compared to 42 gender-matched controls (CON). One symptomatic and one asymptomatic SWITCH patient had abnormal exercise myocardial perfusion; both patients had variant coronary anatomy preoperatively. SWITCH patients had lower VO_2peak (p < 0.01), peak heart rates (p = 0.01), percentages of age-predicted peak heart rates (p < 0.01), and peak oxygen pulses indexed to body surface area (p < 0.01) than CON patients. Exercise testing with myocardial perfusion imaging helped to identify the rare SWITCH patient with coronary insufficiencies. This study demonstrates that exercise testing with myocardial perfusion scans can help identify patients at risk for myocardial events. This study also demonstrated that SWITCH patients have a mildly diminished VO_2peak when compared to CON patients.     

Comparison of Calculated with Measured Oxygen Consumption in Children Undergoing Cardiac Catheterization

Our objective was to compare calculated (LaFarge) with measured oxygen consumption (VO₂) using the AS/3 TM Compact Airway Module M-CAiOVX (Datex-Ohmeda, Helsinki, Finland; AS/3 TM) in children without cardiac shunts in a prospective, observational study. VO₂ was determined at the end of the routine diagnostic and/or interventional catheterization. VO₂ was calculated according to the formula of LaFarge and Miettinen for each child and compared with the measured VO₂. Data were compared using simple regression and Bland Altman analysis. Fifty-two children aged from 0.5 to 16 years (median, 6.9 years) and weighing 3.4 to 59.4 kg (median, 22.9 kg) were investigated. Calculated VO₂ values ranged from 59.0 to 230.8 ml/min, and measured VO₂ values from 62.7 to 282.2 ml/min. Comparison of calculated versus measured VO₂ values revealed a significant correlation (r = 0.90, p < 0.0001). Bias and precision were 8.9 and 48.3 ml/min, respectively (95% limits of agreement: −39.4 to 57.2 ml/min). Comparison of calculated VO₂ in children older than 3 years (n = 41), as restricted to the formula, with measured VO₂, revealed a slightly reduced correlation (r = 0.86, p < 0.0001). Bias and precision were 10.0 and 52.5 ml/min, respectively (95% limits of agreement: –42.4 to 62.5 ml/min). We conclude that calculation of VO₂ by the LaFarge formula does not provide reliable values compared to measured values. In clinical routine, measured rather than calculated VO₂ values should be used for the estimation of cardiac output and related variables.     

Effect of voxelotor on cardiopulmonary testing in youths with sickle cell anemia in a pilot study

Background

Individuals with sickle cell anemia (SCA) exhibit decreased exercise capacity. Anemia limits oxygen-carrying capacity and affects cardiopulmonary fitness. The drug voxelotor raises hemoglobin in SCA. We hypothesized that voxelotor improves exercise capacity in youths with SCA.

Methods

In a single-center, open-label, single-arm, longitudinal interventional pilot study (NCT04581356), SCA patients aged 12 and older, stably maintained on hydroxyurea, were treated with 1500 mg voxelotor daily, and performed cardiopulmonary exercise testing before (CPET#1) and after voxelotor (CPET#2). A modified Bruce Protocol was performed on a motorized treadmill, and breath-by-breath gas exchange data were collected. Peak oxygen consumption (peak VO₂), anaerobic threshold, O₂ pulse, VE/VCO₂ slope, and time exercised were compared for each participant. The primary endpoint was change in peak VO₂. Hematologic parameters were measured before each CPET. Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) surveys were collected.

Results

Ten hemoglobin SS patients aged 12–24 completed the study. All demonstrated expected hemoglobin rise, with average +1.6 g/dL (p = .003) and P₅₀ left shift of average −11 mmHg (p < .0001) with decreased oxygen off-loading at low pO₂. The change in % predicted peak VO₂ from CPET#1 to CPET#2 ranged from −12.8% to +11.3%, with significant improvement of more than 5% in one subject, more than 5% decrease in five subjects, and insignificant change of less than 5% in four subjects. All 10 CGIC and seven of 10 PGIC responses were positive.

Conclusion

In a plot study of 10 youths with SCA, voxelotor treatment did not improve peak VO₂ in 9 out of 10 patients.     

Gas exchange during exercise in obese children

Twenty-three obese children, aged 9 to 14 years, ranging in percentage overweight from 26% to 83% (median 51.6%±16.3%), and 37 normal-weight children, matched for sex, age and height, performed a maximal exercise test on a treadmill. Cardiorespiratory performance was assessed by determination of the ventilatory anaerobic threshold (VAT) expressed in ml O₂/min per kg and as a percent of maximal oxygen uptake (% VO₂max). VAT and VO₂max related to body weight were significantly lower (P<0.01) in the obese than in the normal-weight children. VAT % VO₂max was similar in the two groups. A significant correlation was found between VAT and VO₂max both in the obese (r=0.85) and in the control groups (r=0.79). The habitual level of physical activity was lower in the obese subjects compared to the control subjects (P<0.001). In conclusion our study shows that physical fitness of overweight children is quantitatively lowered and that it can be assessed by VAT. VAT does not require a maximal test and is particularly useful in the ergometric study of subjects with exercise intolerance.Abbreviations AT anaerobic threshold - HR heart rate - VAT ventilatory anaerobic threshold - VCO₂ carbon dioxide output - VE ventilation - VO₂ oxygen uptake - VO₂max maximal oxygen uptake     

The Cause of B-Type Natriuretic Peptide Elevation and the Dose-Dependent Effect of Angiotensin-Converting Enzyme Inhibitor on Patients Late After Tetralogy of Fallot Repair

Patients after surgical repair of tetralogy of Fallot (TOF) may experience various complications that result in neurohormonal activation, including plasma B-type natriuretic peptide (BNP) elevation. Right ventricular (RV) dilation is a frequent complication, and few treatments are available. This study aimed to identify the factor or factors leading to BNP elevation and to clarify the effects of angiotensin-converting enzyme inhibitor (ACE-I) on changes in BNP levels in patients with repaired TOF. Plasma BNP levels and hemodynamic data derived from cardiac catheterization were analyzed. In addition, longitudinal BNP levels and ACE-I dosages were analyzed for patients administered ACE-I. For 31 patients with repaired TOF, who mainly had RV dilation, log BNP levels were significantly correlated with the RV end-diastolic volume index (P = 0.02) as well as ventricular volume and pressure (P < 0.01). For 11 patients medicated with ACE-I, BNP levels were significantly lower at the time of maximal ACE-I dosage than at the time of minimal dosage (P < 0.01). Furthermore, BNP levels decreased as the ACE-I dosage per body weight increased (P < 0.01). In conclusion, elevation of BNP in patients after TOF repair could reflect volume and pressure load in the RV end-diastolic phase, and ACE-I may reduce BNP levels in a dose-dependent manner.     

Cardiorespiratory Exercise Tolerance in Asymptomatic Children with Ebstein's Anomaly

The aim of the study was to evaluate cardiorespiratory exercise tolerance in asymptomatic children with Ebstein's anomaly. Eleven children with a mean age of 9.6 years were prospectively studied by spirometry, cardiopulmonary exercise testing (bicycle ergometer n= 8, treadmill test n= 3), and contrast echocardiography. A right-to-left atrial shunt was detected by contrast echocardiography in 7 children (group 1), whereas no shunt was found in 4 (group 2). VO₂ max was decreased [84.5 (SD = 16.8)] and was strongly correlated to oxygen saturation in group 1 (p < 0.0001). Oxygen saturation at peak uptake was significantly decreased compared to baseline [97.4 (SD = 2.0) vs 90% (SD = 9.5%), p= 0.02] and was significantly lower in group 1 than in group 2 [85.7 (2.2) vs 98.2% (SD = 1.2%), p= 0.03]. Oxygen desaturation was related to a right-to-left atrial shunt (p= 0.01). Decreased VO₂ max was also correlated to the small size of the left ventricle (p= 0.05). We concluded that decreased exercise tolerance in children with asymptomatic Ebstein's anomaly is related to a right-to-left atrial shunt and to a small left ventricle. In case of poor exercise tolerance, a contrast echocardiography should be performed to detect an atrial septal defect.     

Exertional Oscillatory Ventilation During Cardiopulmonary Exercise Test in Fontan Patients with Total Cavopulmonary Connection

Exertional oscillatory ventilation (EOV) has been noted during cardiopulmonary exercise testing (CPX) in patients with heart failure. EOV is a predictor of poor prognosis in adult patients with heart failure. The objective of this study was to clarify the incidence and influence of EOV in Fontan patients. Symptom-limited CPX was performed in 36 Fontan patients at 12.3 ± 4.3 (6.5–24.4) years of age or 5.9 ± 2.0 (3.0–11.2) years after total cavopulmonary connection (TCPC). Mean age at the time of TCPC was 6.3 ± 3.3. All 36 TCPC patients were classified as New York Heart Association classification I or II. They also underwent cardiac catheterization subsequently. EOV was defined as cyclic fluctuations in minute ventilation at rest that persist during effort lasting ≥60% of the exercise duration, with an amplitude ≥15% of the average resting value. EOV was noted in 21 of 36 Fontan patients (58%) with good clinical status. Univariable analysis between Fontan patients with and those without EOV showed significant differences in age at TCPC (p < 0.05), age at CPX (p < 0.02), weight at CPX (p < 0.02), follow-up duration between TCPC and CPX (p < 0.04), ventricular morphology (p < 0.05), and metabolic equivalents (p < 0.05) and peak minute oxygen uptake (VO₂) per body weight (p < 0.05). Multivariable analysis showed that EOV was significantly related to peak VO₂ per kilogram. In conclusion, EOV was frequently noted during exercise in Fontan patients with good clinical status. EOV during exercise seems to be related to higher peak VO₂ per kilogram and younger age at TCPC, which is a contrary result to those for adult patients with chronic heart failure. EOV is a remarkable phenomenon during exercise to compensate for impaired cardiopulmonary function in Fontan patients.     

Aerobic fitness related to cardiovascular risk factors in young children

Low aerobic fitness (maximum oxygen uptake (VO_2PEAK)) is predictive for poor health in adults. In a cross-sectional study, we assessed if VO_2PEAK is related to a composite risk factor score for cardiovascular disease (CVD) in 243 children (136 boys and 107 girls) aged 8 to 11 years. VO_2PEAK was assessed by indirect calorimetry during a maximal exercise test and scaled by body mass (milliliters per minute per kilogram). Total body fat mass (TBF) and abdominal fat mass (AFM) were measured by Dual-energy X-ray absorptiometry. Total body fat was expressed as a percentage of total body mass (BF%) and body fat distribution as AFM/TBF. Systolic and diastolic blood pressure (SDP and DBP) and resting heart rate (RHR) were measured. The mean artery pressure (MAP) and pulse pressure (PP) were calculated. Echocardiography, 2D-guided M-mode, was performed. Left atrial diameter (LA) was measured and left ventricular mass (LVM) and relative wall thickness (RWT) were calculated. Z scores (value for the individual − mean value for group)/SD were calculated by sex. The sum of z scores for DBP, SDP, PP, MAP, RHR, LVM, LA, RWT, BF%, AFM and AFM/TBF were calculated in boys and girls, separately, and used as composite risk factor score for CVD. Pearson correlation revealed significant associations between VO_2PEAK and composite risk factor score in both boys (r = −0.48 P < 0.05) and in girls (r = −0.42, P < 0.05). One-way ANOVA analysis indicated significant differences in composite risk factor score between the different quartiles of VO_2PEAK (P < 0.001); thus, higher VO_2PEAK was associated with lower composite risk factor score for CVD. In conclusion, low VO_2PEAK is associated with an elevated composite risk factor score for CVD in both young boys and girls.     

Plasma Concentrations of Atrial and Brain Natriuretic Peptides and Cyclic Guanosine Monophosphate in Response to Dobutamine Infusion in Patients with Surgically Repaired Tetralogy of Fallot

We examined the plasma concentrations of atrial and brain natriuretic peptides (ANP and BNP) and cyclic guanosine monophosphate (cGMP) during dobutamine infusion and their relationship with hemodynamic parameters in 14 patients with surgically repaired tetralogy of Fallot (TOF). Dobutamine was infused at an initial dose of 5 μg/kg/min and increased by 5 μg/kg/min up to 20 μg/kg/min. The plasma ANP, BNP, and cGMP concentrations were determined before infusion, at the end of each stage, and 15 minutes after discontinuing dobutamine infusion. The plasma concentrations of ANP, BNP, and cGMP were elevated in all patients before dobutamine infusion. The ANP, BNP, and cGMP concentrations decreased in 11 of the 14 patients during dobutamine infusion. In contrast, the plasma ANP and BNP concentrations increased in the remaining 3 patients without a change in the cGMP concentration. The right ventricular pressure and volume were significantly elevated in these patients. The plasma cGMP concentration correlated with the ANP concentration (r= 0.62, p < 0.01) but not the BNP concentration. The plasma ANP concentration during dobutamine infusion correlated with right ventricular systolic pressure (r= 0.71, p < 0.05), mean right atrial pressure (r= 0.29, p < 0.05), and mean pulmonary capillary wedge pressure (r= 0.32, p < 0.05). The BNP concentration correlated with right ventricular volume (r= 0.61, p < 0.05) and systolic pressure (r= 0.46, p < 0.05). In conclusion, rapid changes in ANP, BNP, and cGMP concentrations during dobutamine infusion reflect the changes in atrial and ventricle pressure and volume overload. In surgically repaired TOF, the ANP concentration is affected by right ventricular systolic pressure, right atrial pressure, and pulmonary capillary pressure. Furthermore, the BNP concentration reflects right ventricular pressure and volume overload.     

Habitual Exercise Correlates With Exercise Performance in Patients With Conotruncal Abnormalities

Cardiopulmonary exercise testing (CPET), particularly maximal oxygen consumption (VO₂max), has been used to assess the outcome for patients with palliated congenital heart disease (CHD). Small studies correlating VO₂max with noninvasive imaging measures of ventricular function have led to the hypothesis that VO₂max reflects cardiac performance. In other settings, physical training is associated with increased VO₂max. The authors hypothesized that habitual exercise correlates with VO₂max to a greater degree than ventricular function in a relatively healthy cohort of patients with palliated CHD. The habitual exercise behavior of 208 subjects with conotruncal abnormalities (tetralogy of Fallot, truncus arteriosus, and interrupted aortic arch) at the time of previously performed, study-based CPET and cardiac magnetic resonance imaging (CMR) were retrospectively assessed via questionnaire. The association of VO₂max with habitual exercise duration and CMR measures of ventricular function was tested. Of 208 subjects, 89 (43 %) completed questionnaires, and 78 % of the 89 patients had a concurrent CMR. The mean VO₂max was 76 ± 21 % of that predicted. The CMR-assessed left ventricular ejection fraction was 67.6 ± 7.4 %. The hours of habitual exercise per week correlated with VO₂max (p < 0.001; r ² = 0.14). No association was found between right and left ventricular ejection fraction, cardiac index, or right ventricular end-diastolic volume and VO₂max. In this study, VO₂max correlated with habitual exercise to a greater degree than CMR measurements of ventricular function. These findings highlight the importance of considering the contribution of noncardiac factors when exercise data in both clinical and research settings are interpreted. The contribution of these factors to clinical outcomes deserves further study.     

学龄前儿童听处理评估量表在注意缺陷多动障碍儿童中的应用研究

目的 利用学龄前儿童听处理评估量表(以下称“听处理评估量表”)探讨学龄前注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)儿童的听处理(auditory processing,AP)特征。方法 41例ADHD及41例典型发育(typically developing,TD)儿童进行听处理评估量表、SNAP-Ⅳ评定量表及学龄前持续性注意力测试(Conners’Kiddie Continuous Performance Test,K-CPT)评估，分析比较两组儿童听处理评估量表得分差异及其与SNAP-Ⅳ评定量表和K-CPT结果的相关性。结果 ADHD组儿童听处理评估量表总分及除视觉注意维度外的其他维度得分高于TD组(P<0.05)。ADHD儿童中，SNAP-Ⅳ评定量表的注意缺陷维度得分与听处理评估量表总分(r_{s 30条}=0.531;r_{s 27条}=0.627)及其听觉解码(r_s=0.628)、听觉注意(r_s=0.492)、沟通交流(r     

Mechanographic characteristics of adolescents and young adults with congenital heart disease

The present study comprised 29 adolescents and young adults (15 females, 14 males; aged 14.1–23.9 years) with congenital heart disease (CHD) and focused on the interaction between the biomechanical system and CHD. Individuals were characterized by auxological (height, weight), dynamometric (MIGF, maximal isometric grip force) and mechanograpic parameters (V_max, maximal velocity; PJF, peak jump force; PJP, peak jump power; time of five stand-ups in chair-rising test). PJF, PJP and MIGF were transformed into height-related SD-scores. MIGF-SDS and PJP-SDS were lower in the CHD patients than in reference individuals. PJP-SDS was lower than PJF-SDS. PJP-SDS was correlated to V_max (r = 0.62) and to the time of five-stand-ups in chair-rising (r = −0.62). Transcutaneous oxygen saturation and NYHA classes were correlated to V_max (r = 0.42 and r = −0.57, respectively) and to chair-rising performance (r = −0.60 and r = 0.50, respectively). To conclude, individuals with CHD are characterized by an impaired inter- and intramuscular coordination, which is characterized by a greater decrease in muscular power than muscle force. Conflict of interest: a possible conflict of interest is disclosed.     

Reproducibility of oxygen saturation monitoring during six-minute walk test and exercise stress test in patients with pulmonary arteriovenous malformations associated with hereditary hemorrhagic telangiectasia

Patients with pulmonary arteriovenous malformations (PAVMs) are at risk for multiple complications and require close follow-up. We investigated the reproducibility of the 6-minute walk test (6MWT) and exercise stress test (EST) for the evaluation of low oxygen saturation in patients with PAVMs. Twenty-two patients with PAVMs, most of whom had hereditary hemorrhagic telangiectasia (HHT), participated in a Human Investigations Committee-approved protocol. Patients ranged from 9 to 74 years of age (mean 28) and had a broad spectrum of anatomic subtypes of PAVMs, including focal and diffuse. Standard 6MWT and cycle ergometry EST were both performed twice with adequate rest between tests. Heart rate (HR) and oxygen saturation were measured at the beginning and end of each test. Distance walked and maximum resistance was also recorded. The intraclass correlation coefficients (r_i) at the end of 6MWT were as follows: HR (r_i = 0.940; 95% confidence interval [CI] 0.863–0.975), oxygen saturation (r_i = 0.973; 95% CI 0.933–0.989), and distance (r_i = 0.942; 95% CI 0.867–0.975). The r_is at the end of EST were as follows: HR (r_i = 0.941; 95% CI 0.865–0.975), oxygen saturation (r_i = 0.993; 95% CI 0.982–0.997), and maximum resistance (r_i = 0.941; 95% CI 0.864–0.975). 6MWT and EST were reproducible measures of exercise capacity and oxygen saturation and are potential adjunct tests in the follow-up assessment for patients with PAVMs.     

The effect of human growth hormone therapy on L-(Methyl-2H3)-leucine turnover and urinary pseudouridine concentration in patients with Ullrich-turner syndrome

Abstract The effect of daily human growth hormone (hGH) injections (3 I.U./m²/day) on tissue anabolism was determined in six patients with Ullrich-Turner syndrome (XO) (8.7–19 years of age) using novel techniques such as whole body leucine kinetics during continuous infusion of L-(Methyl-²H₃)-leucine and urinary pseudouridine (5-ribosyluracil) excretion on the one hand and traditional methods like serum urea and amino acid concentrations on the other. Pseudouridine is only found in ribonucleic acid (RNA) and is neither reincorporated nor catabolically broken down and is therefore considered an ideal index of whole body RNA turnover. The mean L-(Methyl-²H₃)-leucine turnover of the six XO patients before hGH was 1.90±0.15 moles/kg per minute. After 3 months of hGH-treatment it had increased in three patients, whereas it had decreased in the other three. The results obtained with the stable isotope technique were correlated with the urinary pseudouridine concentrations (r=0.68;P<0.01). The growth rates were positively correlated with leucine turnover (r=0.63;P<0.02) and urinary pseudouridine concentration (r=0.73;P<0.006) as well as negatively correlated with the serum urea concentrationsr=–0.62;P<0.03). The decrease in the individual serum urea concentrations were tightly correlated with the hGH induced change in growth rate (r=0.90;P<0.01). The individual bone ages were negatively correlated with the hGH induced changes in leucine turnover (r=–0.77;P<0.003) as well as with the urinary pseudouridine concentrations (r=–0.87P<0.0002). The hGH effect on leucine and RNA turnover, showing effectiveness only until a developmental age between 11 and 12 years, leads the discussion of the ideal moment of oestrogen supplementation when girls with Ullrich-Turner syndrome are treated with hGH in early adolescence.Conclusion The protein metabolism of patients with Ullrich-Turner syndrome is influenced by hGH in an age dependent manner. In a clinical setting, pseudouridine, an easily determined derivative of ribonucleic acids, may be able to replace the tedious work with expensive stable isotopes when questions related to tissue anabolism are to be answered.