PMC:3750932 / 57252-69830 JSONTXT

{"project":"2_test","denotations":[{"id":"23829793-15194177-81675468","span":{"begin":252,"end":255},"obj":"15194177"},{"id":"23829793-3605900-81675469","span":{"begin":1171,"end":1174},"obj":"3605900"},{"id":"23829793-3605900-81675470","span":{"begin":1384,"end":1387},"obj":"3605900"},{"id":"23829793-11115457-81675471","span":{"begin":2196,"end":2198},"obj":"11115457"},{"id":"23829793-3175350-81675472","span":{"begin":2199,"end":2202},"obj":"3175350"},{"id":"23829793-19749199-81675473","span":{"begin":2914,"end":2916},"obj":"19749199"},{"id":"23829793-18799981-81675474","span":{"begin":2917,"end":2920},"obj":"18799981"},{"id":"23829793-12119247-81675475","span":{"begin":3885,"end":3888},"obj":"12119247"},{"id":"23829793-19749199-81675476","span":{"begin":4750,"end":4752},"obj":"19749199"},{"id":"23829793-11733397-81675477","span":{"begin":5010,"end":5013},"obj":"11733397"},{"id":"23829793-19749199-81675478","span":{"begin":5140,"end":5142},"obj":"19749199"},{"id":"23829793-19749199-81675479","span":{"begin":5707,"end":5709},"obj":"19749199"},{"id":"23829793-17475953-81675480","span":{"begin":6394,"end":6397},"obj":"17475953"},{"id":"23829793-21947513-81675481","span":{"begin":7125,"end":7128},"obj":"21947513"},{"id":"23829793-18626305-81675482","span":{"begin":7716,"end":7718},"obj":"18626305"},{"id":"23829793-15083767-81675483","span":{"begin":7948,"end":7950},"obj":"15083767"},{"id":"23829793-18279740-81675484","span":{"begin":8402,"end":8405},"obj":"18279740"},{"id":"23829793-18347220-81675485","span":{"begin":8406,"end":8409},"obj":"18347220"},{"id":"23829793-19713419-81675486","span":{"begin":8591,"end":8594},"obj":"19713419"},{"id":"23829793-17242010-81675487","span":{"begin":8595,"end":8598},"obj":"17242010"},{"id":"23829793-17242010-81675488","span":{"begin":8735,"end":8738},"obj":"17242010"},{"id":"23829793-12715285-81675489","span":{"begin":9298,"end":9301},"obj":"12715285"},{"id":"23829793-19555858-81675490","span":{"begin":9750,"end":9751},"obj":"19555858"},{"id":"23829793-17174196-81675491","span":{"begin":11118,"end":11121},"obj":"17174196"},{"id":"23829793-18626305-81675492","span":{"begin":11767,"end":11769},"obj":"18626305"},{"id":"23829793-21680644-81675493","span":{"begin":12358,"end":12361},"obj":"21680644"},{"id":"23829793-21680644-81675494","span":{"begin":12572,"end":12575},"obj":"21680644"},{"id":"T89379","span":{"begin":252,"end":255},"obj":"15194177"},{"id":"T47103","span":{"begin":1171,"end":1174},"obj":"3605900"},{"id":"T35714","span":{"begin":1384,"end":1387},"obj":"3605900"},{"id":"T23702","span":{"begin":2196,"end":2198},"obj":"11115457"},{"id":"T11880","span":{"begin":2199,"end":2202},"obj":"3175350"},{"id":"T66018","span":{"begin":2914,"end":2916},"obj":"19749199"},{"id":"T21496","span":{"begin":2917,"end":2920},"obj":"18799981"},{"id":"T98495","span":{"begin":3885,"end":3888},"obj":"12119247"},{"id":"T71372","span":{"begin":4750,"end":4752},"obj":"19749199"},{"id":"T86895","span":{"begin":5010,"end":5013},"obj":"11733397"},{"id":"T12965","span":{"begin":5140,"end":5142},"obj":"19749199"},{"id":"T27528","span":{"begin":5707,"end":5709},"obj":"19749199"},{"id":"T41815","span":{"begin":6394,"end":6397},"obj":"17475953"},{"id":"T21071","span":{"begin":7125,"end":7128},"obj":"21947513"},{"id":"T79727","span":{"begin":7716,"end":7718},"obj":"18626305"},{"id":"T90797","span":{"begin":7948,"end":7950},"obj":"15083767"},{"id":"T86954","span":{"begin":8402,"end":8405},"obj":"18279740"},{"id":"T13204","span":{"begin":8406,"end":8409},"obj":"18347220"},{"id":"T6699","span":{"begin":8591,"end":8594},"obj":"19713419"},{"id":"T95623","span":{"begin":8595,"end":8598},"obj":"17242010"},{"id":"T88195","span":{"begin":8735,"end":8738},"obj":"17242010"},{"id":"T36842","span":{"begin":9298,"end":9301},"obj":"12715285"},{"id":"T70629","span":{"begin":9750,"end":9751},"obj":"19555858"},{"id":"T96399","span":{"begin":11118,"end":11121},"obj":"17174196"},{"id":"T11390","span":{"begin":11767,"end":11769},"obj":"18626305"},{"id":"T40390","span":{"begin":12358,"end":12361},"obj":"21680644"},{"id":"T97051","span":{"begin":12572,"end":12575},"obj":"21680644"}],"text":"Diagnostic methods\nThe diagnostic process of PAH requires a series of investigations that are intended to make the diagnosis, to clarify the clinical class of PH and the underlying type of PAH and to evaluate the functional and hemodynamic impairment [183]. The detection of PH requires investigations including electrocardiogram, chest radiograph and trans-thoracic echocardiogram. Other conditions which can induce PH will be identified by tests such as pulmonary function tests, arterial blood gases, ventilation and perfusion lung scan, high resolution computed tomography (HR-CT) of the chest and pulmonary angiography. Additional investigations are required for evaluation of PAH severity including exercise testing and hemodynamics. Additional imaging may clarify underlying lung abnormalities. Finally, right heart catheterisation confirms the definite diagnosis.\n\nElectrocardiogram (ECG)\nThe ECG may provide suggestive or supportive evidence of PH by demonstrating right ventricular hypertrophy and strain, and right atrial dilation. Right ventricular hypertrophy and right axis deviation are present in respectively 87% and 79% of patients with idiopathic PAH [105]. Unfortunately, the ECG has low sensitivity and specificity as a screening tool for detecting PH.\n\nChest radiography\nIn 90% of idiopathic PAH patients, chest radiography is abnormal at the time of diagnosis [105]. Findings include central pulmonary arterial dilatation which contrasts with loss of the peripheral blood vessels. Right atrial and ventricular enlargement may be seen in more advanced cases. Chest radiography may help to identify associated moderate-to-severe lung disease or pulmonary venous hypertension due to left heart abnormalities.\n\nPulmonary function test and arterial blood gases\nPulmonary function tests (PFT) will help to assess underlying lung abnormalities. Forced expiratory volume in one second (FEV1) and total lung capacity (TLC) in idiopathic PAH are usually normal or slightly abnormal. Low diffusing capacity of the lung for carbon monoxide (DLCO) has been reported in PAH patients, but is more pronounced in PVOD patients with often severe reductions under 50% of the predicted value [56,184]. Results of arterial blood gases usually show mild hypoxemia and hypocapnia. Severe hypoxemia may be a parameter of underlying PVOD or chronic lung disease.\n\nExercise testing\nThe normal physiologic response of the pulmonary vasculature to exercise consists of distension of pulmonary arteries and arterioles as well as recruitment of previously unused vascular bed. Thus, in health, pulmonary artery pressure rises minimally in response to increased blood flow and pulmonary vascular resistance decreases because of the remodeled vasculature. These mechanisms are impaired in the course of PH. Cardiopulmonary exercise testing (CPET) has been shown to be useful in assessing the severity and prognosis of PAH [15,185]. Several mechanisms are associated: (1) failure to perfuse the ventilated lung, leading to an increase of physiologic dead space and ventilatory requirement; (2) failure to increase cardiac output appropriately in response to exercise, causing an early lactic acidosis, thereby increasing acid ventilatory drive; and (3) exercise-induced hypoxemia increasing the hypoxic ventilatory drive. The ventilatory expired gas abnormalities precipitated by PH are multifactorial and associated with disease severity. CPET assesses and measure the ventilation–perfusion mismatch (i.e. acceptable ventilation/diminished perfusion), reflected by an elevated VD/VT or VE/VCO2 ratio or slope and diminished partial pressure of end-tidal carbon dioxide (PETCO2), and the decreased peak VO2 and VO2 at the ventilatory threshold (VT). Peak VO2, VE/VCO2 ratio or slope or PETCO2, measure during CPET, all demonstrated independent and strong prognostic value as univariate markers [186].\n\nTransthoracic doppler-echocardiography (TTE)\nTTE is a non-invasive screening test for patients with suspected PH. TTE estimates pulmonary artery systolic pressure (sPAP) and may provide additional information about the cause and consequences of PH. The estimation of PAP is based on the peak velocity of the jet of tricuspid regurgitation. The simplified Bernoulli equation describes the relationship of tricuspid regurgitation velocity and the peak pressure gradient of tricuspid regurgitation = 4 x (tricuspid regurgitation velocity). Estimation of PA systolic pressure require to take into account right atrial pressure (PA systolic pressure = tricuspid regurgitation pressure gradient + estimated right atrial pressure). Right atrial pressure cannot be measured and is estimated based on the diameter and respiratory variation of the inferior vena cava [15]. An alternative approach to echocardiographic diagnosis of PH is based on the comparison of tricuspid regurgitation velocity with values reported in a healthy population. Ideally, the influence of age, sex and body mass should be taken into consideration [187]. This method avoids cumulative error but is less directly linked to the accepted hemodynamic definition of PH based on mPAP [15].\nOther echocardiographic variables that might raise or reinforce suspicion of PH independently of tricuspid regurgitation velocity should always be considered. They include an increased velocity of pulmonary valve regurgitation and a short acceleration time of RV ejection into the PA. Increased dimensions of right heart chambers, abnormal shape and function of the interventricular septum, increased RV wall thickness, pericardial effusion and dilated main PA are also suggestive of PH, but these signs are considered to be related to the hemodynamic severity [15].\nBesides identification of PH, TTE also allows a differential diagnosis of the possible causes of pulmonary hypertension. TTE can recognize left heart valvular diseases and myocardial diseases responsible for post-capillary PH, and congenital heart diseases with systemic-to-pulmonary shunts. The venous injection of agitated saline can help to identify patent foramen ovale or small sinus venosus type atrial septal defects. Transesophageal echocardiography is rarely required in the setting of PH.\n\nVentilation/perfusion lung scan\nVentilation/perfusion lung scan should be systematically assessed to screen for CTEPH. Indeed, V/Q lung scan is the method of choice to detect CTEPH [188] and normal V/Q scan can eliminate CTEPH.\n\nHigh resolution computed tomography of the chest\nHigh resolution computed tomography of the chest (HRCT) supplies detailed information about underlying lung parenchyma disease, such as pulmonary emphysema or interstitial lung disease. A number of various pathologic features may be detected on chest HRCT including pericardial effusions and pulmonary artery enlargement, defined by the ratio of the diameter of main pulmonary artery to that of the thoracic aorta \u003e1. In the setting of CTEPH, contrast HRCT of the pulmonary arteries may show changes like complete vessel obstruction, vessel cut-offs, intimal irregularities, incorporated thrombus formations as well as bands and webs [189]. Furthermore, collaterals from bronchial arteries can be identified with this technique. Proximal pulmonary obstruction is displaying about significant and accessible organized fibrous tissue in segmental or subsegmental arteries. If no proximal obstruction or obliteration is noted; lesions are considered to be distal, non-accessible to surgery intervention. In some cases, pulmonary angiography is necessary to differentiate between proximal or distal obstructions. Chest HRCT may also suggest PVOD in the presence of adenopathy mediastinal, ground glass opacities and septal lines [53].\n\nPulmonary angiography\nIn CTEPH, pulmonary angiography may be helpful to determinate surgically accessible form. Typical angiographic findings in CTEPH are complete obstruction, band and webs as well as intimal irregularities [74]. Pulmonary angiography may be also helpful in the setting of fibrosing mediastinitis.\n\nCardiac magnetic resonance imaging\nCardiac magnetic resonance imaging (MRI) allows non invasive evaluation of right ventricular size, morphology and shape. It provides information on right ventricular function and allows non-invasive assessment of blood flow including cardiac output, stroke volume, distensibility of pulmonary artery and right ventricular mass [190,191]. Decreased stroke volume, an increased right ventricular right ventricular end-diastolic volume and a decreased measured at baseline are associated with poor prognosis of disease [192,193]. In addition, it has been demonstrated that deterioration of these parameters at one-year follow-up were also predictors of mortality [193]. Thus cardiac MRI could represent a non-invasive tool to evaluate severity of PAH patients at baseline and during follow-up. Further studies are needed to evaluate the precise place of cardiac MRI in the management of PAH patients.\n\nAbdominal ultrasound scan\nAbdominal ultrasound should be performed in all patients if PH is suspected to exclude portal hypertension or liver disease. When portal hypertension is suspected, the diagnosis can be confirmed during RHC by measurement of an increased gradient between the free and occluded hepatic vein pressure [194].\n\nBlood tests\nSerological tests for HIV, hepatitis B or C serology should be performed to screen for associated diseases. The thyroid hormone measurement may reveal either hyperthyroid dysfunction or autoimmune thyroiditis, frequently encountered in PAH.\n\nRight heart catheterization\nInvasive hemodynamic assessment with right heart catheterization is requested to confirm the diagnosis of PH showing a resting mPAP of ≥25 mmHg and a normal PCWP [2]. This value has been used for selecting patients in all RCTs and registries of PAH, however normal mPAP at rest is around of 14 mmHg, with an upper limit of normal of 20 mm Hg. The significance of a mean PAP between 21 and 24 mmHg is currently unclear. No definition of PH on exercise was currently adopted, because of the large variability of mPAP on exercise in healthy individuals.\nThe assessment of PCWP may allow the distinction between precapillary (normal PCWP ≤15 mmHg) and postcapillary PH (PCWP \u003e15 mm Hg). In post-capillary PH, the last guidelines from the 4th World Symposium (Dana Point) proposed a dichotomy between \"passive\" and \"reactive\" (out-of-proportion) post-capillary PH based on transpulmonary pressure gradient (mPAP–PCWP, respectively ≤ or \u003e 12 mm Hg). Indeed, there is no clear consensus on this definition and the future recommendations arising from the last World Symposium on PH (Nice, 2013) should propose new definition to define these two entities.\nMeasurement values obtained by RHC are PAP (diastolic, mean and systolic), right atrial pressure (RAP), PCWP, right ventricular pressure and cardiac output (CO) preferably by the thermodilution method. In contrast to the thermodilution method, the Fick method is mandatory in patients with suspected CHD. In experienced centres, RHC procedures have low morbidity and mortality rates [195]. Elevated mean right atrial pressure reduced CO and mixed venous oxygen saturation (SVO2) are related to the prognosis of PAH patients.\n\nAssessment of disease severity\nNYHA functional class at baseline or after initiation of epoprostenol treatment, signs of right heart failure, 6-MWD, peak VO2, echocardiographic parameters, hemodynamic parameters and biological tests (hyperuricemia, brain natriuretic peptide, troponin) predict prognosis in idiopathic PAH when assessed at baseline.\nPatients presenting PVOD or PAH associated with CTD (frequently associated with venous involvement) have a worse prognosis than patients with idiopathic PAH [53]. Patients with PAH associated with congenital systemic to pulmonary shunts have a more slowly progressive course than idiopathic PAH patients. Few data are available in other conditions such as HIV infection or portal hypertension. In these circumstances, underlying diseases may contribute to the overall outcome. In clinical practice, the prognostic value of a single variable in the individual patient may be less significant than the value of multiple concordant variables.\nA score has been proposed (REVEAL Registry Risk Score) to evaluate severity of newly diagnosed PAH patients [196]. This score was based on several parameters including subgroups of PAH, renal insufficiency, age \u003e 60 years, NYHA FC, systolic blood pressure, heart rate, 6-MWD, BNP, pericardial effusions, DLCO, RAP and PVR [196].\n"}

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methods\nThe diagnostic process of PAH requires a series of investigations that are intended to make the diagnosis, to clarify the clinical class of PH and the underlying type of PAH and to evaluate the functional and hemodynamic impairment [183]. The detection of PH requires investigations including electrocardiogram, chest radiograph and trans-thoracic echocardiogram. Other conditions which can induce PH will be identified by tests such as pulmonary function tests, arterial blood gases, ventilation and perfusion lung scan, high resolution computed tomography (HR-CT) of the chest and pulmonary angiography. Additional investigations are required for evaluation of PAH severity including exercise testing and hemodynamics. Additional imaging may clarify underlying lung abnormalities. Finally, right heart catheterisation confirms the definite diagnosis.\n\nElectrocardiogram (ECG)\nThe ECG may provide suggestive or supportive evidence of PH by demonstrating right ventricular hypertrophy and strain, and right atrial dilation. Right ventricular hypertrophy and right axis deviation are present in respectively 87% and 79% of patients with idiopathic PAH [105]. Unfortunately, the ECG has low sensitivity and specificity as a screening tool for detecting PH.\n\nChest radiography\nIn 90% of idiopathic PAH patients, chest radiography is abnormal at the time of diagnosis [105]. Findings include central pulmonary arterial dilatation which contrasts with loss of the peripheral blood vessels. Right atrial and ventricular enlargement may be seen in more advanced cases. Chest radiography may help to identify associated moderate-to-severe lung disease or pulmonary venous hypertension due to left heart abnormalities.\n\nPulmonary function test and arterial blood gases\nPulmonary function tests (PFT) will help to assess underlying lung abnormalities. Forced expiratory volume in one second (FEV1) and total lung capacity (TLC) in idiopathic PAH are usually normal or slightly abnormal. Low diffusing capacity of the lung for carbon monoxide (DLCO) has been reported in PAH patients, but is more pronounced in PVOD patients with often severe reductions under 50% of the predicted value [56,184]. Results of arterial blood gases usually show mild hypoxemia and hypocapnia. Severe hypoxemia may be a parameter of underlying PVOD or chronic lung disease.\n\nExercise testing\nThe normal physiologic response of the pulmonary vasculature to exercise consists of distension of pulmonary arteries and arterioles as well as recruitment of previously unused vascular bed. Thus, in health, pulmonary artery pressure rises minimally in response to increased blood flow and pulmonary vascular resistance decreases because of the remodeled vasculature. These mechanisms are impaired in the course of PH. Cardiopulmonary exercise testing (CPET) has been shown to be useful in assessing the severity and prognosis of PAH [15,185]. Several mechanisms are associated: (1) failure to perfuse the ventilated lung, leading to an increase of physiologic dead space and ventilatory requirement; (2) failure to increase cardiac output appropriately in response to exercise, causing an early lactic acidosis, thereby increasing acid ventilatory drive; and (3) exercise-induced hypoxemia increasing the hypoxic ventilatory drive. The ventilatory expired gas abnormalities precipitated by PH are multifactorial and associated with disease severity. CPET assesses and measure the ventilation–perfusion mismatch (i.e. acceptable ventilation/diminished perfusion), reflected by an elevated VD/VT or VE/VCO2 ratio or slope and diminished partial pressure of end-tidal carbon dioxide (PETCO2), and the decreased peak VO2 and VO2 at the ventilatory threshold (VT). Peak VO2, VE/VCO2 ratio or slope or PETCO2, measure during CPET, all demonstrated independent and strong prognostic value as univariate markers [186].\n\nTransthoracic doppler-echocardiography (TTE)\nTTE is a non-invasive screening test for patients with suspected PH. TTE estimates pulmonary artery systolic pressure (sPAP) and may provide additional information about the cause and consequences of PH. The estimation of PAP is based on the peak velocity of the jet of tricuspid regurgitation. The simplified Bernoulli equation describes the relationship of tricuspid regurgitation velocity and the peak pressure gradient of tricuspid regurgitation = 4 x (tricuspid regurgitation velocity). Estimation of PA systolic pressure require to take into account right atrial pressure (PA systolic pressure = tricuspid regurgitation pressure gradient + estimated right atrial pressure). Right atrial pressure cannot be measured and is estimated based on the diameter and respiratory variation of the inferior vena cava [15]. An alternative approach to echocardiographic diagnosis of PH is based on the comparison of tricuspid regurgitation velocity with values reported in a healthy population. Ideally, the influence of age, sex and body mass should be taken into consideration [187]. This method avoids cumulative error but is less directly linked to the accepted hemodynamic definition of PH based on mPAP [15].\nOther echocardiographic variables that might raise or reinforce suspicion of PH independently of tricuspid regurgitation velocity should always be considered. They include an increased velocity of pulmonary valve regurgitation and a short acceleration time of RV ejection into the PA. Increased dimensions of right heart chambers, abnormal shape and function of the interventricular septum, increased RV wall thickness, pericardial effusion and dilated main PA are also suggestive of PH, but these signs are considered to be related to the hemodynamic severity [15].\nBesides identification of PH, TTE also allows a differential diagnosis of the possible causes of pulmonary hypertension. TTE can recognize left heart valvular diseases and myocardial diseases responsible for post-capillary PH, and congenital heart diseases with systemic-to-pulmonary shunts. The venous injection of agitated saline can help to identify patent foramen ovale or small sinus venosus type atrial septal defects. Transesophageal echocardiography is rarely required in the setting of PH.\n\nVentilation/perfusion lung scan\nVentilation/perfusion lung scan should be systematically assessed to screen for CTEPH. Indeed, V/Q lung scan is the method of choice to detect CTEPH [188] and normal V/Q scan can eliminate CTEPH.\n\nHigh resolution computed tomography of the chest\nHigh resolution computed tomography of the chest (HRCT) supplies detailed information about underlying lung parenchyma disease, such as pulmonary emphysema or interstitial lung disease. A number of various pathologic features may be detected on chest HRCT including pericardial effusions and pulmonary artery enlargement, defined by the ratio of the diameter of main pulmonary artery to that of the thoracic aorta \u003e1. In the setting of CTEPH, contrast HRCT of the pulmonary arteries may show changes like complete vessel obstruction, vessel cut-offs, intimal irregularities, incorporated thrombus formations as well as bands and webs [189]. Furthermore, collaterals from bronchial arteries can be identified with this technique. Proximal pulmonary obstruction is displaying about significant and accessible organized fibrous tissue in segmental or subsegmental arteries. If no proximal obstruction or obliteration is noted; lesions are considered to be distal, non-accessible to surgery intervention. In some cases, pulmonary angiography is necessary to differentiate between proximal or distal obstructions. Chest HRCT may also suggest PVOD in the presence of adenopathy mediastinal, ground glass opacities and septal lines [53].\n\nPulmonary angiography\nIn CTEPH, pulmonary angiography may be helpful to determinate surgically accessible form. Typical angiographic findings in CTEPH are complete obstruction, band and webs as well as intimal irregularities [74]. Pulmonary angiography may be also helpful in the setting of fibrosing mediastinitis.\n\nCardiac magnetic resonance imaging\nCardiac magnetic resonance imaging (MRI) allows non invasive evaluation of right ventricular size, morphology and shape. It provides information on right ventricular function and allows non-invasive assessment of blood flow including cardiac output, stroke volume, distensibility of pulmonary artery and right ventricular mass [190,191]. Decreased stroke volume, an increased right ventricular right ventricular end-diastolic volume and a decreased measured at baseline are associated with poor prognosis of disease [192,193]. In addition, it has been demonstrated that deterioration of these parameters at one-year follow-up were also predictors of mortality [193]. Thus cardiac MRI could represent a non-invasive tool to evaluate severity of PAH patients at baseline and during follow-up. Further studies are needed to evaluate the precise place of cardiac MRI in the management of PAH patients.\n\nAbdominal ultrasound scan\nAbdominal ultrasound should be performed in all patients if PH is suspected to exclude portal hypertension or liver disease. When portal hypertension is suspected, the diagnosis can be confirmed during RHC by measurement of an increased gradient between the free and occluded hepatic vein pressure [194].\n\nBlood tests\nSerological tests for HIV, hepatitis B or C serology should be performed to screen for associated diseases. The thyroid hormone measurement may reveal either hyperthyroid dysfunction or autoimmune thyroiditis, frequently encountered in PAH.\n\nRight heart catheterization\nInvasive hemodynamic assessment with right heart catheterization is requested to confirm the diagnosis of PH showing a resting mPAP of ≥25 mmHg and a normal PCWP [2]. This value has been used for selecting patients in all RCTs and registries of PAH, however normal mPAP at rest is around of 14 mmHg, with an upper limit of normal of 20 mm Hg. The significance of a mean PAP between 21 and 24 mmHg is currently unclear. No definition of PH on exercise was currently adopted, because of the large variability of mPAP on exercise in healthy individuals.\nThe assessment of PCWP may allow the distinction between precapillary (normal PCWP ≤15 mmHg) and postcapillary PH (PCWP \u003e15 mm Hg). In post-capillary PH, the last guidelines from the 4th World Symposium (Dana Point) proposed a dichotomy between \"passive\" and \"reactive\" (out-of-proportion) post-capillary PH based on transpulmonary pressure gradient (mPAP–PCWP, respectively ≤ or \u003e 12 mm Hg). Indeed, there is no clear consensus on this definition and the future recommendations arising from the last World Symposium on PH (Nice, 2013) should propose new definition to define these two entities.\nMeasurement values obtained by RHC are PAP (diastolic, mean and systolic), right atrial pressure (RAP), PCWP, right ventricular pressure and cardiac output (CO) preferably by the thermodilution method. In contrast to the thermodilution method, the Fick method is mandatory in patients with suspected CHD. In experienced centres, RHC procedures have low morbidity and mortality rates [195]. Elevated mean right atrial pressure reduced CO and mixed venous oxygen saturation (SVO2) are related to the prognosis of PAH patients.\n\nAssessment of disease severity\nNYHA functional class at baseline or after initiation of epoprostenol treatment, signs of right heart failure, 6-MWD, peak VO2, echocardiographic parameters, hemodynamic parameters and biological tests (hyperuricemia, brain natriuretic peptide, troponin) predict prognosis in idiopathic PAH when assessed at baseline.\nPatients presenting PVOD or PAH associated with CTD (frequently associated with venous involvement) have a worse prognosis than patients with idiopathic PAH [53]. Patients with PAH associated with congenital systemic to pulmonary shunts have a more slowly progressive course than idiopathic PAH patients. Few data are available in other conditions such as HIV infection or portal hypertension. In these circumstances, underlying diseases may contribute to the overall outcome. In clinical practice, the prognostic value of a single variable in the individual patient may be less significant than the value of multiple concordant variables.\nA score has been proposed (REVEAL Registry Risk Score) to evaluate severity of newly diagnosed PAH patients [196]. This score was based on several parameters including subgroups of PAH, renal insufficiency, age \u003e 60 years, NYHA FC, systolic blood pressure, heart rate, 6-MWD, BNP, pericardial effusions, DLCO, RAP and PVR [196].\n"}