Maurice Beghetti

2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS)Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT)

Guidelines summarize and evaluate all available evidence on a particular issue at the time of the writing process, with the aim of assisting health professionals in selecting the best management strategies for an individual patient with a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines and recommendations should help health professionals to make decisions in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate. 2015 ESC/ERS pulmonary hypertension guidelines incorporate changes and adaptations focusing on clinical management http://ow.ly/RiDLb

Bosentan Therapy in Patients With Eisenmenger Syndrome A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study

Background— Eisenmenger syndrome is characterized by the development of pulmonary arterial hypertension with consequent intracardiac right-to-left shunt and hypoxemia in patients with preexisting congenital heart disease. Because Eisenmenger syndrome is associated with increased endothelin expression, patients may benefit from endothelin receptor antagonism. Theoretically, interventions that have some effect on the systemic vascular bed could worsen the shunt and increase hypoxemia. Methods and Results— The Bosentan Randomized Trial of Endothelin Antagonist Therapy-5 (BREATHE-5) was a 16-week, multicenter, randomized, double-blind, placebo-controlled study evaluating the effect of bosentan, a dual endothelin receptor antagonist, on systemic pulse oximetry (primary safety end point) and pulmonary vascular resistance (primary efficacy end point) in patients with World Health Organization functional class III Eisenmenger syndrome. Hemodynamics were assessed by right- and left-heart catheterization. Secondary end points included exercise capacity assessed by 6-minute walk distance, additional hemodynamic parameters, functional capacity, and safety. Fifty-four patients were randomized 2:1 to bosentan (n=37) or placebo (n=17) for 16 weeks. The placebo-corrected effect on systemic pulse oximetry was 1.0% (95% confidence interval, −0.7 to 2.8), demonstrating that bosentan did not worsen oxygen saturation. Compared with placebo, bosentan reduced pulmonary vascular resistance index (−472.0 dyne · s · cm−5; P=0.0383). The mean pulmonary arterial pressure decreased (−5.5 mm Hg; P=0.0363), and the exercise capacity increased (53.1 m; P=0.0079). Four patients discontinued as a result of adverse events, 2 (5%) in the bosentan group and 2 (12%) in the placebo group. Conclusions— In this first placebo-controlled trial in patients with Eisenmenger syndrome, bosentan was well tolerated and improved exercise capacity and hemodynamics without compromising peripheral oxygen saturation.

2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS)Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), Intern…

Guidelines summarize and evaluate all available evidence on a particular issue at the time of the writing process, with the aim of assisting health professionals in selecting the best management strategies for an individual patient with a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines and recommendations should help health professionals to make decisions in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate. 2015 ESC/ERS pulmonary hypertension guidelines incorporate changes and adaptations focusing on clinical management http://ow.ly/RiDLb

Physical activity reduces systemic blood pressure and improves early markers of atherosclerosis in pre-pubertal obese children.

OBJECTIVES The aim of this study was to determine the effects of physical activity on systemic blood pressure (BP) and early markers of atherosclerosis in pre-pubertal obese children. BACKGROUND Hypertension and endothelial dysfunction are premature complications of obesity. METHODS We performed a 3-month randomized controlled trial with a modified crossover design: 44 pre-pubertal obese children (age 8.9 + or - 1.5 years) were randomly assigned (1:1) to an exercise (n = 22) or a control group (n = 22). We recruited 22 lean children (age 8.5 + or - 1.5 years) for baseline comparison. The exercise group trained 60 min 3 times/week during 3 months, whereas control subjects remained relatively inactive. Then, both groups trained twice/week during 3 months. We assessed changes at 3 and 6 months in office and 24-h BP, arterial intima-media thickness (IMT) and stiffness, endothelial function (flow-mediated dilation), body mass index (BMI), body fat, cardiorespiratory fitness (maximal oxygen consumption [VO(2)max]), physical activity, and biological markers. RESULTS Obese children had higher BP, arterial stiffness, body weight, BMI, abdominal fat, insulin resistance indexes, and C-reactive protein levels, and lower flow-mediated dilation, VO(2)max, physical activity, and high-density lipoprotein cholesterol levels than lean subjects. At 3 months, we observed significant changes in 24-h systolic BP (exercise -6.9 + or - 13.5 mm Hg vs. control 3.8 + or - 7.9 mm Hg, -0.8 + or - 1.5 standard deviation score [SDS] vs. 0.4 + or - 0.8 SDS), diastolic BP (-0.5 + or - 1.0 SDS vs. 0 + or - 1.4 SDS), hypertension rate (-12% vs. -1%), office BP, BMI z-score, abdominal fat, and VO(2)max. At 6 months, change differences in arterial stiffness and IMT were significant. CONCLUSIONS A regular physical activity program reduces BP, arterial stiffness, and abdominal fat; increases cardiorespiratory fitness; and delays arterial wall remodeling in pre-pubertal obese children. (Effects of Aerobic Exercise Training on Arterial Function and Insulin Resistance Syndrome in Obese Children: A Randomized Controlled Trial; NCT00801645).

2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension

Nazzareno Galiè (ESC Chairperson), Marc Humbert (ERS Chairperson), Jean-Luc Vachiery, Simon Gibbs, Irene Lang, Adam Torbicki, Gérald Simonneau, Andrew Peacock, Anton Vonk Noordegraaf, Maurice Beghetti, Ardeschir Ghofrani, Miguel Angel Gomez Sanchez, Georg Hansmann, Walter Klepetko, Patrizio Lancellotti, Marco Matucci, Theresa McDonagh, Luc A. Pierard, Pedro T. Trindade, Maurizio Zompatori and Marius Hoeper The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and of the European Respiratory Society (ERS)

Inhaled Nitric Oxide Versus Aerosolized Iloprost in Secondary Pulmonary Hypertension in Children With Congenital Heart Disease Vasodilator Capacity and Cellular Mechanisms

Background —Inhaled nitric oxide (iNO) has been used to assess the vasodilator capacity of the pulmonary vascular bed in children with congenital heart disease and elevated pulmonary vascular resistance. Inhaled iloprost is a pulmonary vasodilator for the long-term treatment of pulmonary hypertension (PHT). Because these 2 vasodilators act through different pathways (release of cGMP or cAMP, respectively), we compared the pulmonary vasodilator capacity of each. Methods and Results —A total of 15 children with congenital heart disease and PHT who had elevated pulmonary vascular resistance (preoperative, n=10; immediately postoperative, n=5) were first given 20 ppm of iNO for 10 minutes; then, after baseline values were reached again, they were given aerosolized iloprost at 25 ng · kg−1 · min−1 for another 10 minutes. Finally, iNO and iloprost were given simultaneously for 10 minutes. With iNO, the pulmonary vascular resistance and systemic vascular resistance ratio decreased from 0.48±0.38 to 0.27±0.16 (P <0.001). Similarly, iloprost decreased the ratio from 0.49±0.38 to 0.26±0.11 (P <0.05). The combination had no additional effect on the resistance ratio. Plasma cGMP increased from 17.6±11.9 to 34.7±21.4 nmol/L during iNO (P <0.01), and plasma cAMP increased from 55.7±22.9 to 65.1±21.2 nmol/L during iloprost inhalation (P <0.05). Conclusions —In children with PHT and congenital heart disease, both iNO and aerosolized iloprost are equally effective in selectively lowering pulmonary vascular resistance through an increase in cGMP or cAMP, respectively. However, the combination of both vasodilators failed to prove more potent than either substance alone. Aerosolized iloprost might be an alternative to iNO for early testing of vascular reactivity and for the postoperative treatment of acute PHT.

Treatment of a persistent postoperative chylothorax with somatostatin

Chylothorax is a rare but potentially serious complication of pediatric cardiac operations. We report the case of a 4-month-old boy who underwent a Senning procedure for correction of D-transposition of the great vessels. A persistent postoperative chylothorax developed, necessitating continuous drainage, despite conservative treatment over 3 weeks. Thereafter, continuous somatostatin infusion for 14 days led to the reduction and finally cessation of chyle production. This treatment allowed early enteral feeding and avoided further surgical intervention.

Short- and Long-Term Effects of Inhaled Iloprost Therapy in Children With Pulmonary Arterial Hypertension

OBJECTIVES This study investigated the short- and long-term outcome of children with pulmonary arterial hypertension (PAH) treated with inhaled iloprost. BACKGROUND Inhaled iloprost has been approved for the treatment of adults with PAH, but little is known about the effects in children with PAH. METHODS We evaluated the acute effects of inhaled iloprost on hemodynamic status and lung function and the response to long-term therapy in 22 children (range 4.5 to 17.7 years) with PAH (idiopathic, n = 12; congenital heart disease, n = 10). Cardiac catheterization, standard lung function testing before and after iloprost inhalation, 6-min walk test, World Health Organization functional class, and hemodynamic parameters were monitored. RESULTS Acute administration of inhaled iloprost lowered mean pulmonary artery pressure equivalent to the response to inhaled nitric oxide with oxygen. Acute iloprost inhalation reduced forced expiratory volume in 1 s and mid-volume forced expiratory flow by 5% and 10%, respectively, consistent with acute bronchoconstriction. At 6 months, functional class improved in 35%, decreased in 15%, and remained unchanged in 50% of children. Sixty-four percent of patients continued receiving long-term iloprost therapy, 36% stopped iloprost, due to lower airway reactivity, clinical deterioration, or death. In 9 patients on chronic intravenous prostanoids, 8 transitioned from intravenous prostanoids to inhaled iloprost, which continued during follow-up. CONCLUSIONS Inhaled iloprost caused sustained functional improvement in some children with PAH, although inhaled iloprost occasionally induced bronchoconstriction. Most patients tolerated the transition from intravenous to inhaled prostanoid therapy. Clinical deterioration, side effects, and poor compliance, owing to the frequency of treatments, could limit chronic treatment in children.

Impaired endothelial and smooth muscle functions and arterial stiffness appear before puberty in obese children and are associated with elevated ambulatory blood pressure

AIMS To determine whether impaired brachial endothelial (flow-mediated dilation, FMD) and smooth muscle function (nitroglycerin-mediated dilation, NTGMD), and remodelling of the common carotid artery (CCA) develop before puberty in obese children. METHODS AND RESULTS Arterial intima-media thickness (IMT), FMD and NTGMD were measured by high-resolution ultrasound in 48 obese and 23 lean pre-pubertal children (8.8 +/- 1.5 years old). We assessed central pulse pressure, incremental elastic modulus (Einc), casual and ambulatory systolic (SBP) and diastolic blood pressure (DBP), and body fatness by DXA. Obese children had significantly lower FMD (4.5 +/- 4.0 vs. 8.3 +/- 1.7%), NTGMD (19.0 +/- 9.0 vs. 25.8 +/- 6.1%), and increased Einc (13.9 +/- 5.2 vs. 10.4 +/- 5.2 mmHg/10(2)), ambulatory SBP (121.3 +/- 12.6 vs. 106.6 +/- 7.1, mmHg), and DBP (69.1 +/- 5.7 vs. 63.7 +/- 4.5) than lean subjects, whereas IMT was not augmented. Ambulatory systolic hypertension was present in 47% of obese subjects. FMD, NTGMD, and Einc were correlated with body fatness, body mass index, and blood pressure (BP). CONCLUSION Impaired endothelial and smooth muscle functions and altered wall material develop before puberty in obese children, however remodelling of the CCA is not yet present. Arterial dysfunction may be considered as the first marker of atherosclerosis and is associated with elevated BP. Ambulatory blood pressure monitoring may be a potential tool to improve risk stratification in obese children.

Pulmonary arterial hypertension: a comparison between children and adults

The characteristics of pulmonary arterial hypertension (PAH), including pathology, symptoms, diagnosis and treatment are reviewed in children and adults. The histopathology seen in adults is also observed in children, although children have more medial hypertrophy at presentation. Both populations have vascular and endothelial dysfunction. Several unique disease states are present in children, as lung growth abnormalities contribute to pulmonary hypertension. Although both children and adults present at diagnosis with elevations in pulmonary vascular resistance and pulmonary artery pressure, children have less heart failure. Dyspnoea on exertion is the most frequent symptom in children and adults with PAH, but heart failure with oedema occurs more frequently in adults. However, in idiopathic PAH, syncope is more common in children. Haemodynamic assessment remains the gold standard for diagnosis, but the definition of vasoreactivity in adults may not apply to young children. Targeted PAH therapies approved for adults are associated with clinically meaningful effects in paediatric observational studies; children now survive as long as adults with current treatment guidelines. In conclusion, there are more similarities than differences in the characteristics of PAH in children and adults, resulting in guidelines recommending similar diagnostic and therapeutic algorithms in children (based on expert opinion) and adults (evidence-based).