Evaluation of the diagnostic and prognostic potential of optical coherence tomography (OCT) of the pulmonary arteries during standardised right heart catheterisation in patients with pulmonary hypertension: a cross-sectional single-centre experience.

Background: Pulmonary hypertension (PH) is diagnosed based on an invasive evaluation of the mean pulmonary artery (PA) pressure. The morphological assessment of the pulmonary arteries was only recently not feasible. With the advent of optical coherence tomography (OCT)-imaging, an accessible tool allows to study PA morphology longitudinally. The primary hypothesis was that OCT distincts the PA structure of PH patients from control subjects. The secondary hypothesis was that PA wall thickness (WT) correlates with the progression of PH. Methods: This is a retrospective monocentric study of 28 paediatric patients with (PH group) and without PH (control group) who had undergone cardiac catheterisation including OCT imaging of the PA branches. OCT parameters analysed were WT and the quotient of WT and diameter (WT/DM) and those were compared between the PH group and the control group. In addition, the OCT parameters were aligned with the haemodynamic parameters to evaluate the potential of OCT as a risk factor for patients with PH. Results: WT and WT/DM in the PH group were significantly higher compared to the control group {WT: 0.150 [0.230, range (R): 0.100-0.330] vs. 0.100 [0.050, R: 0.080-0.130] mm, P<0.001; WT/DM: 0.06 [0.05] vs. 0.03 [0.01], P=0.006}. There were highly significant correlations between WT and WT/DM with the haemodynamic parameters mean pulmonary arterial pressure (mPAP) [Spearman correlation coefficient (rs) =0.702, P<0.001; rs=0.621, P<0.001], systolic pulmonary arterial pressure (sPAP) (rs=0.668, P<0.001; rs=0.658, P<0.001) and WT and pulmonary vascular resistance (PVR) (rs=0.590, P=0.02). Also, there was a significant correlation between WT and WT/DM and the risk factors quotient of mPAP and mean systemic arterial pressure (mSAP) (mPAP/mSAP) (rs=0.686, P<0.001; rs=0.644, P<0.001) and pulmonary vascular resistance index (PVRI) (rs=0.758, P=0.002; rs=0.594, P=0.02). Conclusions: OCT can detect significant differences in WT of the PA in patients with PH. Furthermore, the OCT parameters correlate significantly with haemodynamic parameters and risk factors for patients with PH. More investigations are required to evaluate to what extent the impact of OCT can contribute to the clinical care of children with PH.

Motor outcome, executive functioning, and health-related quality of life of children, adolescents, and young adults after ventricular assist device and heart transplantation.

OBJECTIVE: The aim of the current study is to measure long-term executive function, motor outcome, and QoL in children, adolescents, and young adults after VAD and Htx. METHODS: Patients were examined during routine follow-up. Investigation tools were used as follows: Examination for MND of motor outcomes, Epitrack® for attention and executive functioning, and Kidscreen-52 and EQ-5D-5L questionnaires for QoL. Additional data were retrospectively obtained by an analysis of patient medical records. RESULTS: Out of 145 heart transplant recipients at the department of pediatric cardiology of the University Hospital Munich, 39 were implanted with a VAD between 1992 and 2016. Seventeen (43.6%) patients died before or after Htx; 22 (56.4%) patients were included in our study. Mean age at transplant was 9.52 years (range: 0.58-24.39 years, median 9), and the mean follow-up time after Htx was 6.18 years (range: 0.05-14.60 years, median 5.82). MND examination could be performed in 13 patients (normal MND: n = 11, simple MND: n = 1, complex MND: n = 1). Executive functioning was tested in 15 patients. Two (13.3%) patients had good results, six (40%) average results, three (20%) borderline results, and four (26.7%) impaired results. QoL (Kidscreen n = 7, EQ-5D-5L n = 8) was similar to a healthy German population. CONCLUSION: Motor outcome, executive functioning and QoL in survivors of VAD bridging therapy and Htx can be good, though underlying diseases and therapies are associated with a high risk of cerebral ischemic or hemorrhagic complications.

The risk of infective endocarditis following interventional pulmonary valve implantation: A meta-analysis.

BACKGROUND: Interventional percutaneous pulmonary valve implantation (PPVI) was first reported in 2000. Today, two different valves are certified for this procedure [i.e. Medtronic Melody® valve (Medtronic, Dublin, Ireland) and Edwards Sapien™ valve (Edwards Lifesciences, Irvine, CA, USA)]. For a decade, studies have reported an increasing risk of infective endocarditis (IE) after PPVI; as patients for PPVI are usually younger, even a low annual incidence of IE is important. However, the overall incidence and potential differences between the valves remain unclear. METHODS: A systematic literature search was performed in the databases Medline, Cochrane Library, and Embase including the clinical trials register. The aim was to summarize and compare the cumulative incidence of IE after PPVI. Using a sensitivity analysis we set the incidence rates of the two valve types in ratio with a normal population. RESULTS: A total of 967 publications were identified searching for "pulmonary valve implantation," "PPVI," and 47 publications were used for final analysis. A total 3616 patients with Melody® valves and 501 with Sapien™ valves were included. IE after PPVI occurred in 214 patients with Melody® valves and in 5 patients only with Sapien™ valves. The pooled incidence for Melody® and Sapien™ valves was 4.9% (95% CI: 3.6-6.2) and 1.3% (95% CI: 0.3-2.3), respectively. Chi-square test was significant. The sensitivity analysis showed that the incidence rate ratio was 252.1 (95% CI: 187.6-338.6) for Melody® valves and for Sapien™ valves 2.7 (95% CI: 0.8-9.2). CONCLUSIONS: At present, there is an important difference for the risk of IE after PPVI. To reduce the risk of post PPVI endocarditis, a careful valve selection in favor of the Sapien™ valves seems to be beneficial.

The Creation of an Interatrial Right-To-Left Shunt in Patients with Severe, Irreversible Pulmonary Hypertension: Rationale, Devices, Outcomes.

PURPOSE OF THE REVIEW: Targeted pharmacotherapies did improve survival rates, exercise capacity, and quality of life (QoL) of PAH patients. However, these pharmacological interventions are expensive and not always accessible. In addition, not all patients do respond similarly to these medications and many will continue to deteriorate. This review aims to discuss the beneficial role of an artificial right-to-left shunt and highlights current interventional devices and outcomes. RECENT FINDINGS: Since patients with preexisting atrial shunts or patients with Eisenmenger's disease show better survival rates, improved exercise capacity, and QoL, PAH patients clinically do benefit from an atrial septostomy by reducing signs of right heart failure, improving left heart filling, cardiac output, and systemic oxygen transport despite hypoxia. However, an uncontrolled septostomy with unrestricted right-to-left shunt bears the risk of acute severe desaturation and death. The Atrial Flow Regulator (AFR device, Occlutech®, Sweden) provides an adjustable shunt size with restricted flow and excellent short-term outcomes. Interventional strategies for PAH palliation are on the rise. The novel AFR device provides a durable and safe option for a controlled right-to-left shunting, thus enabling an individualized management.

Creation of a defined and stable Fontan fenestration with the new Occlutech Atrial Flow Regulator (AFR®).

This report describes the first clinical experience with the new Occlutech Atrial Flow Regulator (AFR®) device for implementation of a late Fontan fenestration. The AFR® device secured a defined diameter of the fenestration without spontaneous re-occlusion of this extra-anatomic perforation. This ensured a permanent clinical improvement of our failing Fontan patient.

Differentiation of Impaired From Preserved Hemodynamics in Patients With Fontan Circulation Using Real-time Phase-velocity Cardiovascular Magnetic Resonance.

PURPOSE: Progressive impairment of hemodynamics in patients with Fontan circulation is common, multifactorial, and associated with decreased quality of life and increased morbidity. We sought to assess hemodynamic differences between patients with preserved (preserved Fontans) and those with impaired circulation (impaired Fontans) after pulmonary vasodilation using oxygen and under forced breathing conditions. MATERIALS AND METHODS: Real-time phase-contrast cardiovascular magnetic resonance was performed using non-ECG triggered echo-planar imaging (temporal resolution=24 to 28 ms) in the ascending aorta (AAo) and superior vena cava (SVC)/inferior vena cava (IVC) on room air, after 100% oxygen inhalation (4 L/min; 10 min) and on forced breathing in 29 Fontan patients (17.2±7.3 y) and in 32 controls on room air (13.4±3.7 y). The simultaneously recorded patients' respiratory cycle was divided into 4 segments (expiration, end-expiration, inspiration, and end-inspiration) to generate respiratory-dependent stroke volumes (SVs). The imaging data were matched with physiological data and analyzed with home-made software. RESULTS: The mean SVi (AAo) was 46.1±11.1 mL/m in preserved Fontans versus 30.4±6.2 mL/m in impaired Fontans (P=0.002) and 51.1±6.9 mL/m in controls (P=0.107). The cutoff value for differentiation of Fontan groups was SVi (AAo, end-expiratory) of 32.1 mL/m. After hyperoxygenation, the mean SVi (AAo) increased to 48.7±12.7 mL/m in preserved Fontans (P=0.045) but remained unchanged in impaired Fontans (31.1±5.8 mL/m, P=0.665). Simultaneously, heart rates decreased from 75.2±15.9 to 70.8±16.4 bpm (preserved; P=0.000) but remained unchanged in impaired circulation (baseline: 84.1±9.8 bpm, P=0.612). Compared with physiological respiration, forced breathing increased the maximum respiratory-related cardiac index difference (ΔCImax) in preserved Fontans (SVC: 2.5-fold, P=0.000; and IVC: 1.8-fold, P=0.000) and to a lower extent in impaired Fontans (both veins, 1.5-fold; P(SVC)=0.011, P(IVC)=0.013). There was no impact on mean blood flow. CONCLUSIONS: Oxygen affected the pulmonary vascular system by vasodilation and increased SVi in preserved Fontans but had no effect on impaired Fontans. Forced breathing increased ΔCImax but did not change the mean blood flow by sole activation of the ventilatory pump. End-expiratory aortic SVi represents a valuable measure for classifying the severity of Fontan hemodynamics impairment.

Treatment initiation in paediatric pulmonary hypertension: insights from a multinational registry.

Different treatment options for pulmonary hypertension have emerged in recent years, and evidence-based management strategies have improved quality of life and survival in adults. In children with pulmonary vascular disease, therapeutic algorithms are not so clearly defined; this study determined current treatment initiation in children with pulmonary hypertension in participating centres of a registry. Through the multinational Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension registry, patient demographics, diagnosis, and treatment as judged and executed by the local physician were collected. Inclusion criteria were >3 months and <18 years of age and diagnostic cardiac catheterisation consistent with pulmonary hypertension (mean pulmonary arterial pressure ⩾25 mmHg, pulmonary vascular resistance index ⩾3 Wood units×m2, and mean pulmonary capillary wedge pressure ⩽12 mmHg). At diagnostic catheterisation, 217/244 patients (88.9%) were treatment naïve for pulmonary hypertension-targeted therapy. Targeted therapy was initiated after catheterisation in 170 (78.3%) treatment-naïve patients. A total of 19 patients received supportive therapy, 28 patients were not started on therapy, and 26 patients (10.7%) were on targeted treatment before catheterisation. Among treatment-naïve subjects, treatment was initiated with one targeted drug (n=112, 51.6%), dual therapy (n=39, 18%) or triple-therapy (n=5, 2.3%), and calcium channel blockers with one targeted medication in one patient (0.5%). Phosphodiesterase inhibitors type 5 were used frequently; some patients with pulmonary hypertension related to lung disease received targeted therapy. There is a diverse therapeutic approach for children with pulmonary hypertension with a need of better-defined treatment algorithms based on paediatric consensus for different aetiologies including the best possible diagnostic workup.

Closure of very large PDA with pulmonary hypertension: Initial clinical case-series with the new Occlutech® PDA occluder.

OBJECTIVE: We report our recent experience with the new Occlutech® PDA Occluder, which seems suitable especially for closure of large patent ductus arteriosus (PDA) sizes with elevated pulmonary artery pressure (PAH). BACKGROUND: Although considered a standard procedure in pediatric cath labs, closure of very large PDA (PDA/Aorta ratio > 0.5) and PAH remains a challenge. METHODS/RESULTS: The Occlutech® PDA occluder was used in eight children and adolescents (age 4-16, median 10.75 years), body weight from 14 to 54 kg (median 21 kg) with very large PDA and PAH: PDA diameter was 5-13 mm (median 10 mm); PAP/Aortic pressure ratio was 0.58-0.96. Sufficient occlusion of the PDA was documented by angiography and/or echocardiography in all cases. Four different device sizes were selected: Minimal diameter 6-14 mm (median 12 mm), length 6.3-16 mm (median 14 mm), aortic disc 13-24 mm (median 20 mm), size at the pulmonary end 8-18 mm (median 15 mm). A balloon test occlusion of the PDA was performed in five patients in order to evaulate the decline of pulmonary artery pressure or to delineate the exact anatomy of the PDA. Before release of the device, a careful "wiggle manoevre" was performed to assess the stability of the implanted device and to proof the inability to embolize to the aorta. CONCLUSIONS: With the new Occlutech® PDA Occluder closure of very large PDAs and PAH is feasible and efficient. The wider pulmonary artery end of the Occlutech® PDA Occluder offers enhanced stability and reduces the risk of embolization. © 2016 Wiley Periodicals, Inc.

Feasibility and safety of cardiopulmonary exercise testing in children with pulmonary hypertension.

BACKGROUND: Cardiopulmonary exercise testing helps prognosticate and guide treatment in adults with pulmonary hypertension. Concerns regarding its feasibility and safety limit its use in children with pulmonary hypertension. We aimed to assess the feasibility and safety of cardiopulmonary exercise testing in a large paediatric pulmonary hypertension cohort. METHODS: We reviewed all consecutive cardiopulmonary exercise tests performed between March, 2004 and November, 2013. The exclusion criteria were as follows: height <120 cm, World Health Organization class IV, history of exercise-induced syncope, or significant ischaemia/arrhythmias. Significant events recorded were as follows: patient-reported symptoms, arrhythmias, electrocardiogram abnormalities, and abnormal responses of arterial O2 saturation. RESULTS: A total of 98 children underwent 167 cardiopulmonary exercise tests. The median age was 14 years (inter-quartile range 10-15 years). Peak oxygen uptake was 20.4±7.3 ml/kg/minute, corresponding to 51.8±18.3% of the predicted value. Peak respiratory quotient was 1.08±0.16. All the tests except two were maximal, being terminated prematurely for clinical reasons. Baseline Oxygen saturation was 93.3±8.8% and was 81.2±19.5% at peak exercise. A drop in arterial O2 saturation >20% was observed in 23.5% of the patients. Moreover, five patients (3.0%) experienced dizziness, one requiring termination of cardiopulmonary exercise testing; five children (3.0%) experienced chest pain, with early cardiopulmonary exercise test termination in one patient. No significant arrhythmias or electrocardiogram changes were observed. CONCLUSION: Exercise testing in non-severely symptomatic children with pulmonary hypertension is safe and practical, and can be performed in a large number of children with pulmonary hypertension in a controlled environment with an experienced team. Side-effects were not serious and were resolved promptly with test termination.

Effect of bosentan therapy on ventricular and atrial function in adults with Eisenmenger syndrome. A prospective, multicenter study using conventional and Speckle tracking echocardiography.

BACKGROUND: The effect of bosentan on the ventricular and atrial performance in patients with Eisenmenger syndrome is unclear. In adult patients with Eisenmenger syndrome, we aimed to evaluate the midterm effect of bosentan on physical exercise, ventricular and atrial function, and pulmonary hemodynamics. METHODS: Forty adult patients before and after 24 weeks bosentan therapy underwent 6 min walk test, two-dimensional speckle tracking echocardiography, plasma NT-proBNP measurement and cardiac catheterization. RESULTS: After 24 weeks, bosentan therapy an improvement was observed regarding the 6 min walk distance from a median (quartile 1-quartile 3) of 382.5 (312-430) to 450 (390-510) m (p = 0.0001), NT-proBNP from 527.5 (201-1,691.25) to 369 (179-1,246) pg/ml (p = 0.021), right ventricular mean longitudinal systolic strain from 18 (13-22) to 19 (14.5-25) % (p = 0.004), left ventricular mean longitudinal systolic strain from 16 (12-21) to 17 (16-22) % (p = 0.001), right atrial mean peak longitudinal strain from 26 (18-34) to 28 (22-34) % (p = 0.01) and right atrial mean peak contraction strain from 11 (8-16) to 13 (11-16) % (p = 0.005). The invasively obtained Qp:Qs and Rp:Rs did not significantly change under bosentan therapy. CONCLUSIONS: In adult patients with Eisenmenger syndrome, bosentan therapy improves ventricular and atrial functions resulting in enhancement of physical exercise and reduction in the NT-proBNP level, while the pulmonary vascular resistance does not change substantially.

Real-time magnetic resonance assessment of septal curvature accurately tracks acute hemodynamic changes in pediatric pulmonary hypertension.

BACKGROUND: This study assesses the relationship between septal curvature and mean pulmonary artery pressure and indexed pulmonary vascular resistance in children with pulmonary hypertension. We hypothesized that septal curvature could be used to estimate right ventricular afterload and track acute changes in pulmonary hemodynamics. METHODS AND RESULTS: Fifty patients with a median age of 6.7 years (range, 0.45-16.5 years) underwent combined cardiac catheterization and cardiovascular magnetic resonance. The majority had idiopathic pulmonary arterial hypertension (n=30); the remaining patients had pulmonary hypertension associated with repaired congenital heart disease (n=17) or lung disease (n=3). Mean pulmonary artery pressure and pulmonary vascular resistance were acquired at baseline and during vasodilation. Septal curvature was measured using real-time cardiovascular magnetic resonance. There was a strong correlation between mean pulmonary artery pressure and SCmin at baseline and during vasodilator testing (r=-0.81 and -0.85, respectively; P<0.01). A strong linear relationship also existed between pulmonary vascular resistance and minimum septal curvature indexed to cardiac output both at baseline and during vasodilator testing (r=-0.88 and -0.87, respectively; P<0.01). Change in septal curvature metrics moderately correlated with absolute change in mean pulmonary artery pressure and pulmonary vascular resistance, respectively (r=0.58 and -0.74; P<0.01). Septal curvature metrics were able to identify vasoresponders with a sensitivity of 83% (95% confidence interval, 0.36-0.99) and a specificity of 91% (95% confidence interval, 0.77-0.97), using the Sitbon criteria. Idiopathic pulmonary arterial hypertension subgroup analysis revealed 3 responders with ΔSCmin values of 0.523, 0.551, and 0.568. If the middle value of 0.551 is taken as a cutoff, the approximate sensitivity would be 67% and the specificity would be 93%. CONCLUSIONS: Septal curvature metrics are able to estimate right ventricular afterload and track acute changes in pulmonary hemodynamics during vasodilator testing. This suggests that septal curvature could be used for continuing assessment of load in pulmonary hypertension.

Pediatric pulmonary hypertension.

Pulmonary hypertension (PH) is a rare disease in newborns, infants, and children that is associated with significant morbidity and mortality. In the majority of pediatric patients, PH is idiopathic or associated with congenital heart disease and rarely is associated with other conditions such as connective tissue or thromboembolic disease. Incidence data from the Netherlands has revealed an annual incidence and point prevalence of 0.7 and 4.4 for idiopathic pulmonary arterial hypertension and 2.2 and 15.6 for pulmonary arterial hypertension, respectively, associated with congenital heart disease (CHD) cases per million children. The updated Nice classification for PH has been enhanced to include a greater depth of CHD and emphasizes persistent PH of the newborn and developmental lung diseases, such as bronchopulmonary dysplasia and congenital diaphragmatic hernia. The management of pediatric PH remains challenging because treatment decisions continue to depend largely on results from evidence-based adult studies and the clinical experience of pediatric experts.

Diagnostic evaluation of paediatric pulmonary hypertension in current clinical practice.

Current paediatric pulmonary hypertension (PH) diagnostic algorithms include some testing specifically for paediatrics, but it is unclear if this is used in clinical practice. We describe the current diagnostic workup of the TOPP (Tracking Outcomes and Practice in Paediatric Pulmonary hypertension) registry for suspected PH. We investigated 456 patients enrolled until February 2010. The majority had ECGs (94%), echocardiograms (96%) and/or chest radiographs (89%) performed and these were the noninvasive tests most frequently used for evaluation of suspected PH. No patient had all three tests considered normal, suggesting the potential for the combined use to rule out PH. For evaluation of complications associated with heart catheterisation (HC) we analysed a total of 908 HCs reported until February 2012. Of these, 554 were at diagnosis and 354 in follow-up. Complications were reported in 5.9% with five deaths considered related to HC, suggesting a higher rate of HC complications compared to adult studies. However, current recommendations support HC in paediatric PH. A proper application of the risk/benefit ratio for HC requires further data. Most children did not undergo the diagnostic workup currently recommended for adults, which highlights either incomplete awareness of current guidelines and/or challenges their appropriateness for children.

Prognostic significance of cardiac magnetic resonance imaging in children with pulmonary hypertension.

BACKGROUND: There are very few validated prognostic markers in pediatric pulmonary hypertension. Cardiac MRI is a useful, noninvasive method for determining prognosis in adults. The present study is the first to assess its prognostic value in children. METHODS AND RESULTS: A total of 100 children with pulmonary hypertension (median, 10.4 years; range, 0.5-17.6 years) were evaluated (idiopathic, n=60; repaired congenital heart disease, n=22; miscellaneous, n=18). In all patients, ventricular volumes and great vessel flow were measured. Volumetric data were obtained using retrospectively gated cine imaging (n=37) or real-time imaging (n=63), depending on the patient's ability to hold his or her breath. During a median follow-up of 1.9 years, 11 patients died and 3 received lung transplantation. Of the cardiac MR parameters measured, right ventricular ejection fraction and left ventricular stroke volume index were most strongly predictive of survival on univariate analysis (2.6- and 2.5-fold increase in mortality for every 1-SD decrease, respectively; P<0.05). These results were reflected in good separation of tertile-based Kaplan-Meier survival curves for these variables. CONCLUSIONS: Cardiac MR measures correlate with clinical status and prognosis in children with pulmonary hypertension. Cardiac MR is feasible and may be useful in clinical decision making in pediatric pulmonary hypertension.

Atrial septal defect closure with an Amplatzer septal occluder fenestrated with a coronary stent in a child with pulmonary arterial hypertension.

The presence of an atrial septal defect in pulmonary hypertension has benefits and detractions. Even in idiopathic pulmonary arterial hypertension, a significant left-to-right shunt at atrial level may increase the pulmonary arterial pressure and exacerbate the disease. However, it is well recognised that the presence of an atrial communication may be protective in subgroups with severe disease, allowing maintenance of cardiac output during times of increased pulmonary resistance. In the present paper, we present the case of a young boy with significant idiopathic pulmonary arterial hypertension and an atrial septal defect. We report our technique of septal occlusion using a device to decrease left-to-right shunting with concomitant stent insertion in that device to maintain the potential for right-to-left shunting during times of high pulmonary arterial pressure.

Modulation of pulmonary vascular resistance as a target for therapeutic interventions in Fontan patients: focus on phosphodiesterase inhibitors.

Despite advancements in surgical techniques over the past 20 years, Fontan patients have decreased exercise capacity as a consequence of an inherent inability to adequately increase cardiac output during exercise. They are also affected by several complications that are associated with considerable morbidity and mortality. As the systemic and pulmonary circulations are placed in series without a subpulmonary ventricle propelling blood through the pulmonary vasculature, the systemic venous pressure and the respiratory mechanics are the only forces driving pulmonary blood flow. In Fontan circulation, pulmonary vascular resistance is the single most important factor involved in the limitation of cardiac output and treatments able to decrease pulmonary vascular resistance might conversely improve cardiac output and exercise capacity. In this article we discuss the initial experience with the use of sildenafil in Fontan patients and we discuss the possible mechanisms through which sildenafil might positively act in Fontan circulation.

Clinical features of paediatric pulmonary hypertension: a registry study.

BACKGROUND: Paediatric pulmonary hypertension, is an important cause of morbidity and mortality, and is insufficiently characterised in children. The Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension (TOPP) registry is a global, prospective study designed to provide information about demographics, treatment, and outcomes in paediatric pulmonary hypertension. METHODS: Consecutive patients aged 18 years or younger at diagnosis with pulmonary hypertension and increased pulmonary vascular resistance were enrolled in TOPP at 31 centres in 19 countries from Jan 31, 2008, to Feb 15, 2010. Patient and disease characteristics, including age at diagnosis and at enrolment, sex, ethnicity, presenting symptoms, pulmonary hypertension classification, comorbid disorders, medical and family history, haemodynamic indices, and functional class were recorded. Follow-up was decided by the patients' physicians according to the individual's health-care needs. FINDINGS: 362 of 456 consecutive patients had confirmed pulmonary hypertension (defined as mean pulmonary artery pressure ≥25 mm Hg, pulmonary capillary wedge pressure ≤12 mm Hg, and pulmonary vascular resistance index ≥3 WU/m(-2)). 317 (88%) patients had pulmonary arterial hypertension (PAH), which was idiopathic [IPAH] or familial [FPAH] in 182 (57%), and associated with other disorders in 135 (43%), of which 115 (85%) cases were associated with congenital heart disease. 42 patients (12%) had pulmonary hypertension associated with respiratory disease or hypoxaemia, with bronchopulmonary dysplasia most frequent. Finally, only three patients had either chronic thromboembolic pulmonary hypertension or miscellaneous causes of pulmonary hypertension. Chromosomal anomalies, mainly trisomy 21, were reported in 47 (13%) of patients with confirmed disease. Median age at diagnosis was 7 years (IQR 3-12); 59% (268 of 456) were female. Although dyspnoea and fatigue were the most frequent symptoms, syncope occurred in 31% (57 of 182) of patients with IPAH or FPAH and in 18% (eight of 45) of those with repaired congenital heart disease; no children with unrepaired congenital systemic-to-pulmonary shunts had syncope. Despite severe pulmonary hypertension, functional class was I or II in 230 of 362 (64%) patients, which is consistent with preserved right-heart function. INTERPRETATION: TOPP identifies important clinical features specific to the care of paediatric pulmonary hypertension, which draw attention to the need for paediatric data rather than extrapolation from adult studies. FUNDING: Actelion Pharmaceuticals.

Phrenic nerve injury after image-guided insertion of a tunnelled right internal jugular central venous catheter.

Central venous catheters (CVC) are now commonly inserted by radiologists. Although complications are infrequent, they must be avoided where possible and recognized when they occur. We present a 10-year-old boy who developed right hemidiaphragmatic paralysis, requiring surgical plication, following US-guided insertion of a tunnelled right internal jugular CVC. The needle trajectory for internal jugular puncture must be planned to avoid the phrenic nerve.

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.

Fractal branching quantifies vascular changes and predicts survival in pulmonary hypertension: a proof of principle study.

OBJECTIVES: To develop a non-invasive method of assessing disease severity in pulmonary hypertension by quantifying the overall degree of vascular pruning using fractal geometry. DESIGN: A retrospective analysis of ECG-gated CT pulmonary angiograms. SETTING: A single national referral centre for the investigation and treatment of children with pulmonary hypertension. PATIENTS: Consecutive CT pulmonary angiograms in children and young adults (mean age 10.3 years, range 0.7-19.1) with pulmonary arterial hypertension assessed between January 2007 and April 2009. MAIN OUTCOME MEASURES: The fractal dimension (FD) of skeletonised CT pulmonary angiograms was calculated using the box counting method. The FD was compared with pulmonary vascular resistance, the percentage of predicted 6-min walk distance, WHO functional class and survival. RESULTS: Diagnostic plots confirmed that the pulmonary artery angiograms were all fractal. The FD correlated negatively with the pulmonary vascular resistance index (r=-0.55, p=0.01, n=21) and with WHO functional class (p<0.01, n=31) while it correlated positively with the percentage of predicted 6-min walk distance (r=0.43, p=0.04, n=24). A lower FD was associated with poorer survival (HR 5.6; 95% CI 1.2 to 25; p=0.027) for every SD reduction in FD. CONCLUSION: The FD derived from CT can be used to quantify vascular changes in pulmonary hypertension. This non-invasive technique may be useful in monitoring disease progression and response to therapy.