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Pulmonary hypertension (PH) is defined by a sustained increase in mean pulmonary arterial pressure > 25 mmHg. Due to its widespread availability, echocardiography (ECHO) is used as the first-line imaging modality to detect pulmonary PH and assess right ventricular (RV) function in daily routine. As such, ECHO is the key examination to detect the presence of PH, to provide valuable prognostic information and to give an orientation to therapeutic strategies. In addition to detection and screening, ECHO also provides clues for the differential diagnosis of PH. The present document, based on a consensus of experts, provides practical recommendations for the use of ECHO in the evaluation of PH and of its consequences on the right ventricle.

Pulmonary hypertension (PH) is defined by a sustained increase in mean pulmonary arterial pressure > 25 mmHg. Due to its widespread availability, echocardiography (ECHO) is used as the first-line imaging modality to detect pulmonary PH and assess right ventricular (RV) function in daily routine. As such, ECHO is the key examination to detect the presence of PH, to provide valuable prognostic information and to give an orientation to therapeutic strategies. In addition to detection and screening, ECHO also provides clues for the differential diagnosis of PH. The present document, based on a consensus of experts, provides practical recommendations for the use of ECHO in the evaluation of PH and of its consequences on the right ventricle., Journal Article, Practice Guideline, SCOPUS: re.j, info:eu-repo/semantics/published

Tibetans have been reported to present with a unique phenotypic adaptation to high altitude characterized by higher resting ventilation (VE) and arterial oxygen saturation (SpO2), no excessive polycythemia and lower pulmonary artery pressures (Ppa) compared to other high altitude populations. How this affects exercise capacity is not exactly known. We measured aerobic exercise capacity during an incremental cardiopulmonary exercise test (CPET), lung diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO) at rest, and mean Ppa (mPpa) and cardiac output by echocardiography at rest and at exercise in 13 Sherpas and in 13 acclimatized lowlander controls at the altitude of 5050 m in Nepal. In Sherpas versus lowlanders, SpO2 was 86 ± 1 vs 83 ± 2 %, mean ± SE (P NS), mPpa at rest 19 ± 1 vs 23 ± 1 mmHg (P<0.05), DLCO corrected for hemoglobin 61 ± 4 vs 37 ± 2 ml/min/mmHg (P<0.001), DLNO 226 ± 18 vs 153 ± 9 ml/min/mmHg (P<0.001), maximum oxygen uptake (VO2max) 32 ± 3 vs 28 ± 1 ml/kg/min (P NS) and ventilatory equivalent for carbon dioxide at anaerobic threshold 40 ± 2 vs 48 ± 2 (P<0.001). VO2max was correlated directly to DLCO and inversely to the slope of mPpa-cardiac index relationships in both Sherpas and acclimatized lowlanders. We conclude that Sherpas compared to acclimatized lowlanders have an unremarkable aerobic exercise capacity but with less pronounced pulmonary hypertension, lower ventilatory responses and higher lung diffusing capacity., JOURNAL ARTICLE, SCOPUS: ar.j, info:eu-repo/semantics/published

Pulmonary arterial hypertension (PAH) is a rapidly progressive disease, ultimately leading to right heart failure and death. Accumulating evidence indicates that intervention early in disease progression results in better outcomes than delaying treatment. In this review we will discuss the assessments and strategies that can be used to monitor disease progression and guide clinical management. Many tools, such as symptoms, functional classification, exercise capacity, haemodynamic measures, findings on cardiac imaging and levels of biomarkers, have shown to be prognostic for survival both at diagnosis and during treatment. However, attempts to define goal thresholds have produced a variety of results. Several groups have developed risk calculators to estimate individual patients' mortality risk, but the accuracy of these tools across different patient populations remains unknown. What is clear is the importance of regularly assessing a range of parameters and then tailoring treatment goals to each patient. In addition, the use of a multidisciplinary team approach is crucial in order to support patients through all aspects of managing their condition. There is still an urgent need for prospective collaborative initiatives to assess novel goals and improve treatment strategies that would allow physicians to personalise and optimise clinical management for their patients with PAH., Journal Article, Research Support, Non-U.S. Gov't, Review, SCOPUS: ar.j, info:eu-repo/semantics/published

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We tested the ability of exercise testing to predict not only survival but also time to clinical worsening in idiopathic versus associated pulmonary arterial hypertension (PAH).Hundred thirty-six patients with PAH (85 idiopathic and 51 with associated conditions), underwent cardiopulmonary exercise testing and a 6-minute walk test. Death or transplantation, and clinical worsening events were recorded.Thirty-two patients died and 4 had lung transplantation. At univariate analysis, PAH patients survival was associated with oxygen uptake (VO2) at peak exercise and at anaerobic threshold, ventilatory equivalent for CO2 (VEVCO2) at anaerobic threshold (at), VE/VCO2slope and distance walked. Time to clinical worsening was associated with peakVO2 and VO2at, VEVCO2at, end-tidal CO2 partial pressure measured at anaerobic threshold, peakO2 pulse, increase in O2pulse and distance walked. At multivariable analysis, distance walked and VEVCO2at predicted survival, and only peakVO2 predicted time to clinical worsening. The ROC curve-derived cut-off values were 305 m for the 6-min walk distance, 54 for VEVCO2at and 11.6 mL·Kg(-1).min for peakVO2. In the subgroup of associated PAH, no variable independently predicted survival or clinical worsening.We conclude several exercise variables predict survival and clinical stability in idiopathic PAH. Exercise variables are less accurate predictors of outcome in associated PAH., JOURNAL ARTICLE, SCOPUS: ar.j, info:eu-repo/semantics/published

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12e réunion commune de la Société de Néphrologie et de la Société Francophone de Dialyse (Bruxelles, 28/9 au 1/10/2010), info:eu-repo/semantics/published

Altitude exposure is associated with decreased exercise capacity and increased pulmonary vascular resistance (PVR). Echocardiographic measurements of pulmonary haemodynamics and a cardiopulmonary exercise test were performed in 13 healthy subjects at sea level, in normoxia and during acute hypoxic breathing (1 h, 12% oxygen in nitrogen), and in 22 healthy subjects after acclimatisation to an altitude of 5,050 m. The measurements were obtained after randomisation, double-blinded to the intake of placebo or the endothelin A receptor blocker sitaxsentan (100 mg·day(-1) for 7 days). Blood and urine were sampled for renal function measurements. Normobaric as well as hypobaric hypoxia increased PVR and decreased maximum workload and oxygen uptake (V'(O(2),max)). Sitaxsentan decreased PVR in acute and chronic hypoxia (both p<0.001), and partly restored V'(O(2),max), by 30 % in acute hypoxia (p<0.001) and 10% in chronic hypoxia (p<0.05). Sitaxsentan-induced changes in PVR and V'(O(2),max) were correlated (p = 0.01). Hypoxia decreased glomerular filtration rate and free water clearance, and increased fractional sodium excretion. These indices of renal function were unaffected by sitaxsentan intake. Selective endothelin A receptor blockade with sitaxsentan improves mild pulmonary hypertension and restores exercise capacity without adverse effects on renal function in hypoxic normal subjects., Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

Lung carbon monoxide (CO) transfer and pulmonary capillary blood volume (Vc) at high altitudes have been reported as being higher in native highlanders compared to acclimatised lowlanders but large discrepancies appears between the studies. This finding raises the question of whether hypoxia induces pulmonary angiogenesis. Eighteen highlanders living in Bolivia and 16 European lowlander volunteers were studied. The latter were studied both at sea level and after acclimatisation to high altitude. Membrane conductance (Dm(CO)) and Vc, corrected for the haemoglobin concentration (Vc(cor)), were calculated using the NO/CO transfer technique. Pulmonary arterial pressure and left atrial pressures were estimated using echocardiography. Highlanders exhibited significantly higher NO and CO transfer than acclimatised lowlanders, with Vc(cor)/VA and Dm(CO)/VA being 49 and 17% greater (VA: alveolar volume) in highlanders, respectively. In acclimatised lowlanders, Dm(CO) and Dm(CO)/VA values were lower at high altitudes than at sea level. Echocardiographic estimates of cardiac output and pulmonary arterial pressure were significantly elevated at high altitudes as compared to sea level. The decrease in Dm(CO) in lowlanders might be due to altered gas transport in the airways due to the low density of air at high altitudes. The disproportionate increase in Vc in Andeans compared to the change in Dm(CO) suggests that the recruitment of capillaries is associated with a thickening of the blood capillary sheet. Since there was no correlation between the increase in Vc and the slight alterations in haemodynamics, this data suggests that chronic hypoxia might stimulate pulmonary angiogenesis in Andeans who live at high altitudes., Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

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A right heart catheterization with reversibility testing is recommended for the diagnosis and treatment of pulmonary arterial hypertension. In this 24 years-old woman, the inhalation of 5 microg iloprost transiently decreased mean pulmonary artery pressure from 62 to 36 mmHg and pulmonary vascular resistance from 11.0 to 4.9 Wood units, meeting the criteria of a "positive response". The echocardiographic examination showed normalization of right heart chamber dimensions and of the right ventricular performance (Tei) index. Pulsed tissue Doppler imaging of the right ventricle showed a decrease in the isovolumic relaxation time from 102 to 73 ms, and an increase of the E/A ratio from 0.72 to 1.38, together with marked improvements in mid-apical free wall systolic strain and strain rate. A positive response to reversibility testing of pulmonary arterial hypertension may be associated with quasi normalization of right ventricular function, in spite of still elevated pulmonary artery pressure., Case Reports, Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

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Chapitre 1. Introduction, Doctorat en sciences médicales, info:eu-repo/semantics/nonPublished

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We previously reported on the partial prevention of experimental shunt-induced pulmonary arterial hypertension (PAH) by the nonselective endothelin (ET) ET-A/ET-B receptor antagonist bosentan. As the respective roles of the ET-A and ET-B receptor signaling in the pathobiology of the disease remain undefined, we investigated the effects of selective ET-A receptor blockade by sitaxsentan in the same early stage PAH model. Twenty-one 3-wk-old piglets were randomized to placebo or sitaxsentan therapy (1.5 mg/kg/d), after anastomosis of the left subclavian artery to the pulmonary arterial trunk or after a sham operation. Three months later, the animals underwent a hemodynamic evaluation, followed by pulmonary tissue sampling for morphometry and real-time-quantitative-PCR for ET-1, angiopoietin-1, and bone morphogenetic receptor (BMPR) signaling molecules. Three months of left to right shunting induced an increase in pulmonary vascular resistance (PVR) and medial thickness, an overexpression of ET-1, ET-B receptor, and angiopoietin-1, and a decreased expression of BMPR-2 and BMPR-1A. Pretreatment with sitaxsentan prevented shunt-induced increase in PVR and decreased medial thickness by 64%. Sitaxsentan therapy completely prevented the decreased expression of BMPR-2 and limited the overexpression of ET-1, ET-B and angiopoietin-1, and the decreased expression of BMPR-1A. In conclusion, selective ET-A receptor blockade partially prevents shunt-induced PAH. © International Pediatrics Research Foundation, Inc. 2007. All Rights Reserved.

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The use of an exercise stress test in the diagnosis or evaluation of pulmonary hypertension rests on the assumption that multipoint mean pulmonary artery pressure (mPpa)-flow (Q) plots are superior to isolated pulmonary vascular resistance determinations for the evaluation of the functional state of the pulmonary circulation. A multipoint mPpa-Q relationship is best described by a linear approximation and, as such, characterized by an extrapolated pressure intercept and by a slope. Both are dependent on the method used to increase flow. The slope is higher and the pressure intercept lower when exercise is used to increase flow, rather than unilateral pulmonary artery balloon occlusion or low-dose dobutamine. This is because of exercise-induced pulmonary vasoconstriction. The steepest slopes, i.e. the highest pressures at a given flow, are obtained by resistive exercise (handgrip) when compared with dynamic exercise (cycling) because of systemic vascular resistance and intrathoracic pressure changes. Since systolic, diastolic, and mean pulmonary artery pressures are tightly correlated and since in experienced hands, systolic pulmonary artery pressures and cardiac output are reliably measured using Doppler echocardiography, mPpa-Q lines can be obtained non-invasively. The exercise stress test for non-invasive diagnosis of pulmonary hypertension may be particularly useful for the detection of early disease and for more accurate quantification of pulmonary vascular changes induced by disease progression and/or therapeutic interventions. © The European Society of Cardiology 2007. All rights reserved., SCOPUS: ar.j, info:eu-repo/semantics/published

The symptoms of pulmonary hypertension are explained by a decrease in cardiac output caused by an afterload-induced right ventricular (RV) failure. However, the standard haemodynamic evaluation of pulmonary hypertension, with measurements of mean pulmonary vascular pressures and cardiac output, does not capture the determinants of RV function. Right ventricular afterload can be measured either as a hydraulic load calculated from spectral analysis of pulmonary artery pressure and flow waves, or as a maximal wall tension estimated from instantaneous ventricular pressure, volume, and wall thickness measurements. The adequacy of ventricular adaptation to afterload can be assessed by a measurement of the matching of systolic function to arterial elastance. The difficulty in measuring instantaneous RV volume is overcome using a single-beat method, which derives a systolic pressure-volume relationship from instantaneous RV pressure and an integration of pulmonary arterial flow. On such a pressure-volume curve, it is easy to determine graphically end-systolic elastance (Ees, end-systolic pressure on end-systolic volume), as a load-independent measure of contractility, and arterial elastance (E a, end-systolic pressure on stroke volume), as a measure of afterload. The optimal value of the Ees/Ea ratio, compatible with flow output at a minimal energy cost, is between 1 and 2. Patients with severe pulmonary hypertension present with a decreased elastance ratio, in spite of an adaptative increase in systolic function, which underscores that RV failure in the face of increased afterload is a relative notion. Further studies are needed to confirm that right ventriculo-arterial decoupling accounts for a decreased aerobic exercise capacity by a limitation of cardiac output adaptation to peripheral demand. © The European Society of Cardiology 2007. All rights reserved., SCOPUS: ar.j, info:eu-repo/semantics/published

We previously reported on the partial prevention of experimental shunt-induced pulmonary arterial hypertension (PAH) by the nonselective endothelin (ET) ET-A/ET-B receptor antagonist bosentan. As the respective roles of the ET-A and ET-B receptor signaling in the pathobiology of the disease remain undefined, we investigated the effects of selective ET-A receptor blockade by sitaxsentan in the same early stage PAH model. Twenty-one 3-wk-old piglets were randomized to placebo or sitaxsentan therapy (1.5 mg/kg/d), after anastomosis of the left subclavian artery to the pulmonary arterial trunk or after a sham operation. Three months later, the animals underwent a hemodynamic evaluation, followed by pulmonary tissue sampling for morphometry and real-time-quantitative-PCR for ET-1, angiopoietin-1, and bone morphogenetic receptor (BMPR) signaling molecules. Three months of left to right shunting induced an increase in pulmonary vascular resistance (PVR) and medial thickness, an overexpression of ET-1, ET-B receptor, and angiopoietin-1, and a decreased expression of BMPR-2 and BMPR-1A. Pretreatment with sitaxsentan prevented shunt-induced increase in PVR and decreased medial thickness by 64%. Sitaxsentan therapy completely prevented the decreased expression of BMPR-2 and limited the overexpression of ET-1, ET-B and angiopoietin-1, and the decreased expression of BMPR-1A. In conclusion, selective ET-A receptor blockade partially prevents shunt-induced PAH., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

Right ventricular function is frequently abnormal in patients with systemic sclerosis, but whether this is related to pulmonary vascular complications of the disease is unclear. Standard echocardiography with tissue Doppler imaging was performed at rest and during exercise for the study of right ventricular function and pulmonary circulation in 25 consecutive systemic sclerosis patients and in 13 age-matched healthy controls. When compared with the controls, the patients had no difference in systolic right ventricular pressure gradient, but a decreased pulmonary flow acceleration time, and increased right ventricular free wall thickness and end-diastolic dimensions. At the tricuspid annulus, the E maximal velocity was decreased (8.9 +/- 4 versus 11.7 +/- 2.3 cm.s(-1)) and the isovolumic relaxation time corrected to RR interval was increased (6.5 +/- 2.9 versus 4.5 +/- 2.5%). The tissue Doppler imaging profile at the mitral annulus was similar in both groups. At exercise, 18 patients had a decreased maximum workload and cardiac output, no change in systolic right ventricular pressure gradient, but an increase in the slope of pulmonary artery pressure/flow relationships. These results suggest that patients with systemic sclerosis may present with latent pulmonary hypertension as a likely cause of right ventricular diastolic dysfunction, as revealed by stress echocardiography and tissue Doppler imaging., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

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Aerobic exercise capacity is decreased at altitude because of combined decreases in arterial oxygenation and in cardiac output. Hypoxic pulmonary vasoconstriction could limit cardiac output in hypoxia. We tested the hypothesis that acetazolamide could improve exercise capacity at altitude by an increased arterial oxygenation and an inhibition of hypoxic pulmonary vasoconstriction. Resting and exercise pulmonary artery pressure (Ppa) and flow (Q) (Doppler echocardiography) and exercise capacity (cardiopulmonary exercise test) were determined at sea level, 10 days after arrival on the Bolivian altiplano, at Huayna Potosi (4,700 m), and again after the intake of 250 mg acetazolamide vs. a placebo three times a day for 24 h. Acetazolamide and placebo were administered double-blind and in a random sequence. Altitude shifted Ppa/Q plots to higher pressures and decreased maximum O(2) consumption ((.)Vo(2max)). Acetazolamide had no effect on Ppa/Q plots but increased arterial O(2) saturation at rest from 84 +/- 5 to 90 +/- 3% (P < 0.05) and at exercise from 79 +/- 6 to 83 +/- 4% (P < 0.05), and O(2) consumption at the anaerobic threshold (V-slope method) from 21 +/- 5 to 25 +/- 5 ml.min(-1).kg(-1) (P < 0.01). However, acetazolamide did not affect (.)Vo(2max) (from 31 +/- 6 to 29 +/- 7 ml.kg(-1).min(-1)), and the maximum respiratory exchange ratio decreased from 1.2 +/- 0.06 to 1.05 +/- 0.03 (P < 0.001). We conclude that acetazolamide does not affect maximum exercise capacity or pulmonary hemodynamics at high altitudes. Associated changes in the respiratory exchange ratio may be due to altered CO(2) production kinetics., SCOPUS: ar.j, info:eu-repo/semantics/published

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