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there have been significant therapeutic developments in HP&#44; which have been collected in very recently published European guidelines&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">3&#44;4</span></a> This article is a clinical update mainly on PAH&#44; and its objective is to provide an update on the knowledge and developments of the pathogenesis&#44; diagnosis and treatment of this disease&#44; from a practical perspective for clinicians&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Definitions</span><p id="par0020" class="elsevierStylePara elsevierViewall">The diagnosis of PAH is based on hemodynamic criteria and therefore requires the implementation of right cardiac catheterization&#46; The hemodynamic parameters that need to be present for the diagnosis are as follows&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0025" class="elsevierStylePara elsevierViewall">Mean pulmonary artery pressure &#40;mPAP&#41; 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the difference between the diastolic pressure of the pulmonary artery and the pulmonary capillary wedge pressure&#93;&#41;&#46; This parameter helps reclassify those patients with PH and pulmonary capillary wedge pressure &#62;15<span class="elsevierStyleHsp" style=""></span>mmHg into 2 groups&#58; isolated postcapillary PH&#44; if the DPG is &#60;7<span class="elsevierStyleHsp" style=""></span>mmHg&#44; and combined PH &#40;precapillary and postcapillary&#41;&#44; if the DPG is &#8805;7<span class="elsevierStyleHsp" style=""></span>mmHg&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">3</span></a> The latter group has greater vascular remodeling and mortality and replaces the previously named &#8220;disproportionate PH&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">6</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Another important aspect incorporated into the guidelines is the identification of a risk group&#44; 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what has changed&#63;</span><p id="par0060" class="elsevierStylePara elsevierViewall">The classification into 5 groups &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41; remains with few changes in terms of groups 2 and 3&#46; A new term has been suggested for group 4&#58; chronic thromboembolic PH and other pulmonary artery obstructions&#46; For group 5 &#40;unclear multifactorial mechanisms&#41;&#44; the most relevant issue is the inclusion of an unusual hemodynamic condition&#44; segmental PH&#44; which occurs in patients with congenital heart disease &#40;e&#46;g&#46;&#44; tricuspid or pulmonary atresia&#41;&#44; in which only a specific area of the lung irrigated by aortopulmonary collateral vessels is affected&#46; This group also includes PH secondary to chronic hemolytic anemia &#40;previously belonging to group 1&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">1</span></a> especially represented by sickle cell anemia&#44; because the histological changes typical of vasculopathy &#40;plexiform lesions&#41; and the hemodynamic characteristics that define PAH have not been detected&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">10&#8211;12</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Group 1 can be associated with numerous diseases &#40;such as human immunodeficiency virus infection&#44; portal hypertension secondary to liver disease&#44; connective tissue diseases&#44; schistosomiasis and congenital heart disease&#41; and hereditary&#47;familial or idiopathic forms&#46; Although there have not been significant advances in this group&#39;s classification&#44; a number of developments have been incorporated&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#40;A&#41;</span><p id="par0070" class="elsevierStylePara elsevierViewall">New mutations associated with the development of hereditary PAH have been found&#44; specifically&#8230; &#40;1&#41; the mutation of caveolin-1 &#40;CAV1&#41;&#44; a membrane protein abundantly present in endothelial lung cells&#59; &#40;2&#41; the mutation of KCNK3&#44; a protein member-3 of the superfamily of potassium channels&#59; and &#40;3&#41; the mutation of Smad 9 &#40;mothers against decapentaplegic 9&#41;&#44; a protein which belongs to the superfamily of transforming growth factor &#946; &#40;TGF-&#946;&#41;&#46; Even then&#44; approximately 80&#37; of patients with PAH have a BMPR2 &#40;bone morphogenetic protein receptor 2&#41; mutation&#44; which also is part of the TGF-&#946; superfamily&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#40;B&#41;</span><p id="par0075" class="elsevierStylePara elsevierViewall">New drugs have been identified as potential causes of PAH&#46; These findings are conclusive for benfluorex&#44; a derivative of fenfluramine used as a hypoglycemic agent&#44; and has already been withdrawn from European markets&#46; There are also unequivocal data linking the use of serotonin reuptake inhibitors during pregnancy and the development of persistent PH in newborns&#46; Other potential associations include the use of dasatinib &#40;tyrosine kinase inhibitor used for treating chronic myeloproliferative syndromes&#41;&#44; amphetamine mimetics &#40;methylphenidate&#44; phentermine&#44; ropinirole and mazindol&#41; and a possible relationship with interferon &#945; and &#946;&#44; due to the fact that they induce the release of endothelin 1 in the pulmonary endothelial cells&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#40;C&#41;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis&#44; as well as persistent PH of the newborn&#44; are now subgroups of group 1 &#40;1&#8242; and 1&#8243;&#44; respectively&#41;&#46;</p></li></ul></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Epidemiology</span><p id="par0085" class="elsevierStylePara elsevierViewall">The PH of group 2 is considered the most common &#40;present in up to 60&#8211;70&#37; of patients with left ventricular dysfunction&#41; and is&#44; generally&#44; mild to moderate&#46; Within group 1&#44; the disease most frequently associated with PAH globally is schistosomiasis&#44; although it is not prevalent in the western world&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">3</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">In Europe&#44; the prevalence of PAH is estimated between 15 and 60 cases per million inhabitants&#44; and the incidence rate is 5&#8211;10 cases per million individuals&#47;year&#46; Fifty percent of cases are hereditary&#44; idiopathic or secondary to drugs&#46; Among the diseases that predispose patients to the development of PAH&#44; connective tissue diseases are the most common&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">13</span></a> The prevalence of PH and PAH in Spain is estimated at 19&#46;2 and 16 cases per million inhabitants&#44; respectively&#46; In the PAH group&#44; the prevalence rates for idiopathic PAH&#44; associated with congenital heart disease&#44; connective tissue diseases and toxic oil syndrome are 5&#44; 6&#44; 3&#44; 2&#46;5 and 0&#46;5 cases per million inhabitants&#44; respectively&#46; Additionally&#44; the incidence rate for PAH appears to be somewhat lower than the European mean&#44; the latter of which is 3&#46;7 cases per million inhabitants&#47;year&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">14</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">The large national registries&#44; such as the United States REVEAL registry and the French registry&#44; have enabled data collection on the survival of these patients observing that the prognosis worsens when there is reduced cardiac output &#40;i&#46;e&#46;&#44; a cardiac index &#60;2&#46;8<span class="elsevierStyleHsp" style=""></span>L&#47;min&#47;m<span class="elsevierStyleSup">2</span>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">15</span></a> The Spanish registry showed that survival at 1&#44; 3 and 5 years for patients with PAH was 87&#37;&#44; 75&#37; and 65&#37;&#44; respectively&#46; This registry also observed that being male and an increase in right atrial pressure conferred an ominous prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">14</span></a> Regardless of the study population&#44; the leading cause of PAH-related death &#40;50&#37; of cases&#41; is secondary right-sided heart failure&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">16</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Lastly&#44; if a subanalysis is performed of the various PAH-related diseases&#44; there is a notable poor prognosis associated with scleroderma&#44; which represents 61&#37; of cases of PAH related to connective tissue diseases in Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">14</span></a> Survival at 5 years for these patients is 8-fold lower than that for patients with scleroderma without PAH&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">17</span></a></p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Pathophysiology&#58; beyond the vessel</span><p id="par0105" class="elsevierStylePara elsevierViewall">In recent years&#44; the pathogenesis of PAH has been recognized as entailing complex interactions&#46; Dysregulation between the innate and acquired immune system produces an autoimmune response that&#44; through various soluble proinflammatory molecules&#44; acts on the lung vascular wall&#44;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">18</span></a> resulting in the classically known changes of endothelial dysfunction&#44; vasoconstriction&#44; proliferation with endothelial remodeling and in situ thrombosis&#46; These conditions ultimately produce progressive narrowing of the pulmonary vessels&#44; which increases vascular resistance and therefore PAP&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">19</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">The paradigm of this immunologic disorder consists of patients with scleroderma-associated PAH&#46; Studies have shown that these patients frequently have anti-angiotensin type-1 receptor &#40;anti-AT1R&#41; antibodies and anti-endothelin type-A receptor &#40;anti-ET<span class="elsevierStyleInf">A</span>R&#41; antibodies&#44; which are also useful as prognostic markers&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">20</span></a> However&#44; we still do not know whether they are the cause or effect of PAH&#44; of the pathogenic effects of hypoxia or of the effect of certain genetic determinants as potential triggers of this immune dysregulation&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">The immunopathology studies&#44; which traditionally have focused on pulmonary artery smooth muscle&#44; currently delve more into the role of pulmonary endothelial cells and fibroblasts&#44; from which the metabolic theory of PAH emerges&#46; This theory suggests that the cellular phenotype of PAH &#40;mitochondrial hyperpolarization&#44; reduction in mitochondrial reactive oxygen species&#44; increase in intracytoplasmic calcium and histone acetylation suppression&#41; could be due to mitochondrial oxidative phosphorylation inhibition&#44; specifically of glucose oxidation&#46; This inhibition results in a proinflammatory and antiapoptotic condition&#44; which promotes cell proliferation in the pulmonary arteries&#46; There is evidence &#40;in rodent models&#41; that these disorders could be the cause of PAH&#44; which opens a new way of understanding the disease and the possibility for new therapeutic pathways&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">21</span></a></p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Diagnosis</span><p id="par0120" class="elsevierStylePara elsevierViewall">The clinical manifestations results from the right ventricular dysfunction&#46; Exertional dyspnea is the earliest manifestation &#40;85&#37; of patients&#41;&#46; In terms of additional examinations&#44; the electrocardiogram &#40;ECG&#41; usually shows an axis deviation toward the right &#40;&#62;90&#176;&#41; and signs of atrial and right ventricular growth &#40;p &#8220;pulmonale&#8221;&#44; R &#8805;7<span class="elsevierStyleHsp" style=""></span>mm in V1&#44; R&#47;S &#8805;1 in V1&#41; in advanced stages&#46; However&#44; the ECG lacks sufficient sensitivity &#40;55&#37;&#41; and specificity &#40;70&#37;&#41; as a screening technique&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">22</span></a> The chest radiography results are usually abnormal in more than 90&#37; of patients at the time of diagnosis&#46; An increase can be observed in the size of the pulmonary arteries &#40;right interlobar pulmonary artery &#62;16<span class="elsevierStyleHsp" style=""></span>mm&#41;&#44; narrowing of the peripheral vasculature and cardiomegaly at the expense of the right chambers&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Echocardiogram</span><p id="par0125" class="elsevierStylePara elsevierViewall">ECG helps measure systolic PAP&#44; which depends on the presence of tricuspid regurgitation&#46; In general&#44; systolic PAP values &#62;40<span class="elsevierStyleHsp" style=""></span>mmHg are considered the cutoff for indicating right cardiac catheterization&#46; The latest European guidelines recommend assigning a PAH probability level &#40;low&#44; medium or high&#41; based on the echocardiographic findings &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; With these data&#44; only those patients who have risk factors or diseases associated with PAH and a medium to high echocardiographic probability should undergo additional tests&#44; including right cardiac catheterization&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall">The most useful feature of the echocardiogram lies in its ability to rule out signs of left-sided heart disease &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41; and to assess poor prognostic markers of right ventricular systolic function&#44;<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">23&#8211;25</span></a> such as pericardial effusion&#44; a right atrial area &#62;18<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleSup">2</span>&#44; an eccentricity index &#62;1&#46;1 and a reduction in tricuspid annular plane systolic excursion&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">26</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Pulmonary function tests and 6-minute walking test</span><p id="par0135" class="elsevierStylePara elsevierViewall">Spirometry helps rule out the presence of underlying bronchopulmonary diseases&#46; Moreover&#44; a low reading on the diffusing capacity of the lungs for carbon monoxide test &#40;&#60;45&#37; of the reference value&#41; entails a poor outcome&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The 6-minute walking test &#40;6MWT&#41; is the most standardized test for measuring the functional capacity and&#44; until a few years ago&#44; was the main variable for assessing the treatment response in clinical trials&#46; Those patients with PAH who walked more than 330<span class="elsevierStyleHsp" style=""></span>m in this test and those who had a maximal oxygen consumption at maximum effort of more than 15<span class="elsevierStyleHsp" style=""></span>mL&#47;kg&#47;min in a stress test had greater survival&#46; In contrast&#44; a reduction of &#62;10&#37; in terms of the baseline oxygen saturation during the 6MWT is an indicator of severity&#46;<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">27&#44;28</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Ventilation&#47;perfusion lung scintigraphy</span><p id="par0145" class="elsevierStylePara elsevierViewall">This test should be performed in all patients with PH to rule out the forms secondary to chronic thromboembolic pulmonary hypertension&#46; The test has higher sensitivity than computed tomography pulmonary angiography &#40;CT angiography&#41;&#46; Its diagnosis allows for the possibility of functional recovery and even healing through pulmonary endarterectomy&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">29</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">CT angiography and high-resolution CT</span><p id="par0150" class="elsevierStylePara elsevierViewall">In addition to the typical structural signs of PH &#40;a diameter of the main pulmonary artery in the bifurcation &#62;29<span class="elsevierStyleHsp" style=""></span>mm and a pulmonary artery to aorta index &#62;1&#41;&#44; this is a complementary test to ventilated-perfusion scintigraphy for diagnosing forms secondary to chronic thromboembolic disease&#44; especially for the assessment prior to pulmonary endarterectomy&#46; CT angiography can be useful in assessing vasculitis and pulmonary arteriovenous malformations&#46; Both high-resolution CT and CT angiography can provide information on the parenchyma&#39;s condition and are useful when suspecting veno-occlusive disease&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">3</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Cardiac magnetic resonance imaging</span><p id="par0155" class="elsevierStylePara elsevierViewall">This test is the best tool for assessing right ventricular structure and function&#46; It helps obtain information on the ejection volume&#44; cardiac output&#44; bulging of the interventricular septum and the RV mass ratio&#46; A number of these findings&#44; such as an end-diastolic volume of the right ventricle &#62;88<span class="elsevierStyleHsp" style=""></span>mL&#47;m<span class="elsevierStyleSup">2</span>&#44; indicate a poor prognosis&#46; Magnetic resonance angiography also helps assess pulmonary circulation parameters and the dilation and mean flow velocity of the pulmonary artery and the pulmonary vascular resistance&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">30</span></a> In addition to the prognostic value&#44; cardiac MRI enables a more reliable follow-up than with echocardiogram&#44; which&#44; in considerable measure&#44; is observer-dependent&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Biomarkers</span><p id="par0160" class="elsevierStylePara elsevierViewall">The most useful markers are natriuretic peptides &#40;brain natriuretic peptide &#91;BNP&#93; and N-terminal brain natriuretic propeptide &#91;NT-proBNP&#93;&#41;&#46; Values higher than 150<span class="elsevierStyleHsp" style=""></span>pg&#47;mL of BNP or higher than 1800<span class="elsevierStyleHsp" style=""></span>pg&#47;mL of NT-proBNP are predictors of severity and are closely associated with right ventricular dysfunction&#46; Their outpatient monitoring can be useful for assessing the treatment response&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Treatment</span><p id="par0165" class="elsevierStylePara elsevierViewall">The European guidelines<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">3</span></a> recommend stratifying patients with PAH into 3 risk groups of disease progression&#46; The objective is to reach a state of low risk of progression &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41; and improve the patients&#8217; quality of life&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">3&#44;26&#44;31&#44;32</span></a> Comprehensive patient treatment requires a complex and multidisciplinary strategy&#44; which includes 3 basic aspects&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#40;1&#41;</span><p id="par0170" class="elsevierStylePara elsevierViewall">General measures&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#40;2&#41;</span><p id="par0175" class="elsevierStylePara elsevierViewall">Specific drug therapy of the PAH&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#40;3&#41;</span><p id="par0180" class="elsevierStylePara elsevierViewall">Surgical treatment&#46;</p></li></ul></p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">General measures</span><p id="par0185" class="elsevierStylePara elsevierViewall">Diuretics need to be employed at appropriate dosages to maintain euvolemia&#44; along with oxygen therapy to correct hypoxemia &#40;SpO<span class="elsevierStyleInf">2</span> goal &#8805;90&#37;&#41;&#46; Digoxin may also be employed&#44; especially in those patients with right-sided heart failure and low output and those with atrial arrhythmia&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">3&#44;26&#44;31&#44;32</span></a> The role of anticoagulation is uncertain&#44; except in those patients with idiopathic PAH&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">33</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">Other support measures include psychosocial support&#44; prenatal guidance and avoiding strenuous or isometric exercise because these can precipitate syncope&#46; A restricted salt diet is recommended&#44; as is being up to date on vaccinations&#44; of which the influenza and pneumococcal vaccinations are especially important&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">32</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Specific therapy</span><p id="par0195" class="elsevierStylePara elsevierViewall">There are 3 major drug groups for treating PAH&#44; each of which has a specific therapeutic target &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#41;&#46;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#40;1&#41;</span><p id="par0200" class="elsevierStylePara elsevierViewall">Prostaglandin analogs</p><p id="par0205" class="elsevierStylePara elsevierViewall">Prostacyclin &#40;prostaglandin I<span class="elsevierStyleInf">2</span>&#41; causes pulmonary vasodilation through the synthesis of cyclic adenosine monophosphate&#46; In the 1990s&#44; the first clinical trials with a prostacyclin analog&#44; epoprostenol&#44; showed improvement in symptoms&#44; exercise capacity&#44; quality of life and hemodynamic parameters&#44; as well as a reduced mortality&#44; in a period of only 12 weeks&#46; Epoprostenol was the first drug authorized for the treatment of PAH and is still considered the most effective&#46; However&#44; its short half-life&#44; instability at room temperature&#44; high cost and intravenous administration &#40;IV&#41; continue to limit its use&#46; The EPITOME-2 study recently showed the efficacy and tolerance of a new formulation with excipients of arginine and sucrose &#40;epoprostenol AS&#41;&#44; instead of the excipients of glycine and mannitol &#40;epoprostenol GM&#41; in the standard formulation&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">34</span></a> This new formulation gives it stability at room temperature of up to 72<span class="elsevierStyleHsp" style=""></span>h&#44; compared with the 12<span class="elsevierStyleHsp" style=""></span>h of the standard formulation&#44; which translates into greater convenience for the patient who has to reconstitute and load the epoprostenol solution&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">There are other currently available prostanoids&#58; treprostinil &#40;subcutaneous perfusion or IV&#44; inhaled or oral&#41; and iloprost &#40;inhaled&#41;&#46; The effects of these drugs as a whole are dose-dependent&#44; and their use is normally limited to functional classes III&#8211;IV&#46;</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">&#40;2&#41;</span><p id="par0215" class="elsevierStylePara elsevierViewall">Endothelin receptor antagonists &#40;ERA&#41;</p><p id="par0220" class="elsevierStylePara elsevierViewall">High levels of endothelin-1 cause vasoconstriction and endothelial proliferation&#46; ERAs counteract this effect by binding to the endothelin receptors &#40;receptors A and B&#41; and are administered orally&#46; Bosentan showed its efficacy by improving the distance traveled in the 6MWT and decreasing clinical worsening in 16 weeks&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">35</span></a> Ambrisentan&#44; a selective ERA &#40;endothelin A receptor&#41;&#44; and macitentan&#44; a nonselective ERA&#44; have a better pharmacokinetic profile&#44; which allows for their administration in a single dose&#46; The Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcomes compared macitentan against a placebo and showed a reduction in disease progression&#44; including death&#44; and clinical deterioration&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">36</span></a> These benefits were observed both in patients who had not undergone treatment and those who had already undergone specific therapy for PAH&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">&#40;3&#41;</span><p id="par0225" class="elsevierStylePara elsevierViewall">Phosphodiesterase-5 inhibitors &#40;PDE5i&#41; and soluble guanylate cyclase stimulants</p><p id="par0230" class="elsevierStylePara elsevierViewall">Although they are 2 groups of drugs with different targets&#44; both act on the nitric oxide pathway&#46; Nitric oxide is a potent vasodilator and induces an increase in cyclic guanosine monophosphate and degrades by the action of PDE5&#46; In PAH&#44; there is reduced expression of nitric oxide synthase&#46; The two PDE5i approved for treating PAH&#44; sildenafil and tadalafil&#44; increase nitric oxide levels preventing their degradation by PDE5&#46;</p></li></ul></p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0235" class="elsevierStylePara elsevierViewall">Riociguat&#44; which stimulates soluble guanylate cyclase&#44; directly increases cyclic guanosine monophosphate levels independently of nitric oxide&#44; has shown a benefit in terms of exercise capacity&#44; distance traveled in the 6MWT&#44; reduction in pulmonary vascular resistances and delayed clinical worsening&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">37</span></a> This drug is also the only one approved for treating PH associated with chronic thromboembolism&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">38</span></a> The concomitant use of PDE5i and riociguat is contraindicated due to the risk of hypotension&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Combined therapy</span><p id="par0240" class="elsevierStylePara elsevierViewall">Sequential therapy with a single drug has been employed in clinical practice&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">39</span></a> A meta-analysis that included 6 clinical trials showed that combined therapy decreased the risk of clinical worsening by 52&#37;&#44; significantly increased &#40;22<span class="elsevierStyleHsp" style=""></span>m&#41; the distance traveled in the 6MWT and improved the hemodynamic parameters&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">40</span></a> These changes were achieved without increasing the risk of adverse events when compared with the control group but had no effect on overall mortality&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">The Bosentan Randomized Trial of Endothelin Antagonist Therapy-2 initially failed to demonstrate an improvement when using combined therapy with epoprostenol and bosentan&#44; compared with epoprostenol in monotherapy&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">41</span></a> More recently&#44; the Ambrisentan and Tadalafil in Patients with Pulmonary Arterial Hypertension study&#44; which compared combined therapy with ambrisentan and tadalafil against monotherapy with ambrisentan or tadalafil in patients with PAH of WHO functional class II or III&#44; showed a 50&#37; reduction in the primary objective &#40;the sum of death&#44; hospitalization&#44; PAH progression or unsatisfactory clinical condition&#41; in the first group&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">42</span></a> The study also showed an improved capacity for exercise&#44; improved NT-proBNP levels and improved clinical stage&#46; While the international guidelines for PAH management recommend the use of sequential therapy&#44; the latest European guidelines advocate initial combined therapy in WHO functional class IV&#46; In functional classes II and III&#44; both monotherapy and combined therapy are reasonable options&#46; For combined therapy&#44; the guidelines recommend the combination of tadalafil and ambrisentan&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">3</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Surgical treatment</span><p id="par0250" class="elsevierStylePara elsevierViewall">In the 1980s&#44; transplantation was the only treatment available for PAH&#46; Currently&#44; this procedure is reserved for patients who&#44; despite undergoing optimal medical treatment&#44; show disease progression&#46; The technique achieves a survival rate at 5 years of 50&#8211;75&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">43</span></a> The main indication for including a patient on a transplantation list is the presence of refractory symptoms &#40;WHO FC-III&#8211;IV&#41; despite combined triple therapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">3&#44;31</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">Additionally&#44; other techniques have been successful as a bridge to transplantation or as palliative treatment for those patients who are not candidates for transplantation&#46; These techniques include balloon atrial septostomy and pulmonary artery denervation&#46; Balloon atrial septostomy acts by mechanically decompressing the right chambers through the creation of an interatrial opening&#44; thereby allowing for a right&#8211;left shunt&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">1&#44;32&#44;44</span></a> This translates into improved right cardiac output and oxygen transport&#44; reduced right atrial pressure and lower sympathetic hyperactivity&#44; especially in patients with WHO FC-IV&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">45</span></a> However&#44; careful preoperative selection should be performed to reduce perioperative mortality&#46; Balloon atrial septostomy should be avoided in terminal patients&#44; such as those with a right atrial pressure &#8805;20<span class="elsevierStyleHsp" style=""></span>mmHg or an oxygen saturation &#8804;85&#37; in environmental air&#46; In regards to pulmonary artery denervation&#44; a study that included 23 patients in a single center reported significant improvement in the hemodynamic parameters and the distance traveled in the 6MWT after this procedure&#46;</p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflict of interest</span><p id="par0260" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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              "titulo" => "Ventilation&#47;perfusion lung scintigraphy"
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            0 => "Pulmonary hypertension"
            1 => "Pulmonary arterial hypertension"
            2 => "Review"
            3 => "Endothelin receptor antagonist"
            4 => "Phosphodiesterase type 5 inhibitors"
            5 => "Prostacyclin analogs"
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            0 => "Hipertensi&#243;n pulmonar"
            1 => "Hipertensi&#243;n arterial pulmonar"
            2 => "Revisi&#243;n"
            3 => "Antagonista del receptor de endotelina"
            4 => "Inhibidores de la fosfodiesterasa tipo 5"
            5 => "An&#225;lagos de prostaciclina"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Pulmonary arterial hypertension is a rare and progressive disease that mainly affects the pulmonary arterioles &#40;precapillary&#41;&#44; regardless of the triggering etiology&#46; The prevalence of pulmonary hypertension and pulmonary arterial hypertension in Spain is estimated at 19&#46;2 and 16 cases per million inhabitants&#44; respectively&#46; The diagnosis of pulmonary arterial hypertension is based on hemodynamic criteria &#40;mean pulmonary artery pressure &#8805;25<span class="elsevierStyleHsp" style=""></span>mmHg&#44; pulmonary capillary wedge pressure &#8804;15<span class="elsevierStyleHsp" style=""></span>mmHg and pulmonary vascular resistance &#62;3 Wood units&#41; and therefore requires the implementation of right cardiac catheterisation&#46; Sequential therapy with a single drug has been used in clinical practice&#46; However&#44; recent European guidelines recommend combined initial therapy in some situations&#46; This review conducts a critical update of our knowledge of this disease according to the latest guidelines and recommendations&#46;</p></span>"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La hipertensi&#243;n arterial pulmonar es una enfermedad rara y progresiva que afecta principalmente a las arteriolas pulmonares &#40;precapilar&#41;&#44; independientemente de la etiolog&#237;a desencadenante&#46; En Espa&#241;a se estima que la prevalencia de hipertensi&#243;n pulmonar y de hipertensi&#243;n arterial pulmonar es de 19&#44;2 y 16 casos por mill&#243;n de habitantes&#44; respectivamente&#46; El diagn&#243;stico de hipertensi&#243;n arterial pulmonar se basa en criterios hemodin&#225;micos &#40;presi&#243;n media de la arteria pulmonar &#8805;25<span class="elsevierStyleHsp" style=""></span>mmHg&#44; presi&#243;n de enclavamiento capilar pulmonar &#8804;15<span class="elsevierStyleHsp" style=""></span>mmHg&#44; y resistencia vascular pulmonar &#62;3 unidades Wood&#41; y por tanto requiere la realizaci&#243;n de un cateterismo cardiaco derecho&#46; En la pr&#225;ctica cl&#237;nica se ha utilizado la terapia secuencial con un solo f&#225;rmaco&#46; Sin embargo&#44; las recientes gu&#237;as europeas recomiendan la terapia combinada de inicio en algunas situaciones&#46; En esta revisi&#243;n se realiza una actualizaci&#243;n cr&#237;tica de los conocimientos sobre esta enfermedad de acuerdo a las &#250;ltimas gu&#237;as y recomendaciones&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Please cite this article as&#58; Chew CRM&#44; Batres SA&#44; Blanco JJR&#46; Actualizaci&#243;n en hipertensi&#243;n arterial pulmonar&#46; Rev Clin Esp&#46; 2016&#59;216&#58;436&#8211;444&#46;</p>"
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          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; PH&#44; pulmonary hypertension&#59; PAH&#44; pulmonary arterial hypertension&#59; HIV&#44; human immunodeficiency virus&#59; CTED&#44; chronic thromboembolic disease&#59; CKD&#44; chronic kidney disease&#59; EIF2AK4&#44; eukaryotic translation initiation factor 2-alpha kinase 4&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Modified from Gali&#232; et al&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">3</span></a></p>"
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group no&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Associated diseases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1&#46; PAH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;1 Idiopathic<br>1&#46;2 Hereditary &#40;BMPR2 mutation or other&#41;<br>1&#46;3 Drugs and toxins<br>1&#46;4 Associated with&#58;<br><span class="elsevierStyleHsp" style=""></span>1&#46;4&#46;1 Connective tissue diseases<br><span class="elsevierStyleHsp" style=""></span>1&#46;4&#46;2 HIV<br><span class="elsevierStyleHsp" style=""></span>1&#46;4&#46;3 Portal hypertension<br><span class="elsevierStyleHsp" style=""></span>1&#46;4&#46;4 Congenital heart disease<br><span class="elsevierStyleHsp" style=""></span>1&#46;4&#46;5 Schistosomiasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1&#8242;&#46; Pulmonary veno-occlusive disease and&#47;or pulmonary capillary hemangiomatosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#8242;&#46;1 Idiopathic<br>1&#8242;&#46;2 Hereditary &#40;EIF2AK4 mutation or other&#41;<br>1&#8242;&#46;3 Drugs&#44; toxins and radiation-induced<br>1&#8242;&#46;4 Associated with connective tissue diseases or HIV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1&#8242;&#8242;&#46; Persistent PH of the newborn&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2&#46; PH secondary to left-sided heart disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;1 Left ventricular systolic dysfunction<br>2&#46;2 Left ventricular diastolic dysfunction<br>2&#46;3 Valvular heart disease<br>2&#46;4 Inflow&#47;outlet tract obstruction<br>2&#46;5 Pulmonary vein stenosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3&#46; Secondary PH in pulmonary disease and&#47;or hypoxia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;1 Chronic obstructive pulmonary disease<br>3&#46;2 Diffuse interstitial lung disease<br>3&#46;3 Mixed lung disease &#40;e&#46;g&#46;&#44; restrictive and obstructive&#41;<br>3&#46;4 Sleep-related respiratory disorders<br>3&#46;5 Alveolar hypoventilation syndromes<br>3&#46;6 Long-term high altitude exposure<br>3&#46;7 Lung development disorders&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">4&#46; PH secondary to CTED or pulmonary artery obstruction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;1 CTED<br>4&#46;2 Other causes of obstruction&#58; intravascular tumors such as angiosarcoma&#44; arteritis&#44; hydatidosis&#44; and congenital pulmonary artery stenosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">5&#46; PH of multifactorial or undetermined mechanism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;1 Hematologic disorders&#58; chronic hemolytic anemia&#44; splenectomy&#44; myeloproliferative syndromes<br>5&#46;2 Systemic disorders&#58; sarcoidosis&#44; lymphangioleiomyomatosis&#44; pulmonary histiocytosis<br>5&#46;3 Metabolic disorders&#58; Gaucher&#39;s disease&#44; glycogenosis&#44; thyroid diseases<br>5&#46;4 Others&#58; CKD&#44; segmental PH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Peak velocity of tricuspid regurgitation &#40;m&#47;s&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Other signs of pulmonary hypertension<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Degree of ultrasound probability&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#8804;2&#46;8 or not measurable&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#8804;2&#46;8 or not measurable&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2&#46;9&#8211;3&#46;4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not required&nbsp;\t\t\t\t\t\t\n
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Ratio of the right and left ventricle diameters &#62;1&#59; flattening of the interventricular septum &#40;left ventricle eccentricity index &#62;1&#46;1&#41;&#59; diameter of the pulmonary artery &#62;25<span class="elsevierStyleHsp" style=""></span>mm&#59; protodiastolic velocity of pulmonary regurgitation &#62;2&#46;2<span class="elsevierStyleHsp" style=""></span>cm&#47;s&#59; Doppler acceleration time of the right ventricular outflow tract &#60;105<span class="elsevierStyleHsp" style=""></span>ms or midsystolic notch&#59; right atrium area &#62;18<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleSup">2</span>&#59; inferior vena cava diameter &#62;21<span class="elsevierStyleHsp" style=""></span>mm with reduced inspiratory collapse &#40;&#60;20&#37; with deep breath or &#60;50&#37; with superficial breath&#41;&#46;</p> <p class="elsevierStyleNotepara" id="npar0010">Modified from Gali&#232; et al&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">3</span></a></p>"
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Echocardiographic probability of pulmonary hypertension in symptomatic patients with suspected disease&#46;</p>"
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          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; PAH&#44; pulmonary arterial hypertension&#59; PVH&#44; pulmonary venous hypertension&#59; RV&#44; right ventricle&#59; LA&#44; left atrium&#59; E&#47;A ratio&#44; ratio between the velocity of the rapid and early filling phase &#40;early&#41; and the velocity of the late atrial contraction phase in the mitral valve measured by Doppler flow&#59; E&#47;e&#8242; lateral&#44; ratio of the early mitral filling velocity and the mitral protodiastolic tissue velocity&#59; PCWP&#44; pulmonary capillary wedge pressure&#59; PADP&#44; pulmonary artery diastolic pressure&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Modified from Gali&#232; et al&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">3</span></a></p>"
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Parameter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PAH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PVH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Echocardiogram</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Size of the RV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Increased&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Can be increasing&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Size of the LA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Increased&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>RA&#47;LA ratio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Increased&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal &#40;LA<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>RA&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Interventricular septum&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Bulges from right to left&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Bulges from left to right&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Systolic deceleration of the RV outflow tract&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Common&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rare&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>E&#47;A ratio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Lateral e&#8242;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Reduced&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lateral E&#47;e&#8242;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Hemodynamics</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Aortic pressure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal or low&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal or high&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>PCWP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8804;15<span class="elsevierStyleHsp" style=""></span>mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;5<span class="elsevierStyleHsp" style=""></span>mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>PADP&#8211;PCWP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;7<span class="elsevierStyleHsp" style=""></span>mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;5<span class="elsevierStyleHsp" style=""></span>mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Difference between arterial and pulmonary venous hypertension&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at4"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; 6MWT&#44; 6-minute walking test&#59; BNP&#44; brain natriuretic peptide&#59; CI&#44; cardiac index&#59; MRI&#44; magnetic resonance imaging&#59; NT-proBNP&#44; amino-terminal fraction of the brain natriuretic propeptide&#59; RAA&#44; right atrial area&#59; RAP&#44; right atrial pressure&#59; SvO<span class="elsevierStyleInf">2</span>&#44; venous oxygen saturation&#59; VO<span class="elsevierStyleInf">2</span>&#44; oxygen consumption&#59; VE&#47;VCO<span class="elsevierStyleInf">2</span>&#44; ventilatory equivalent for carbon dioxide&#59; FC-WHO&#44; functional class of the World Health Organization&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Prognostic factor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Low risk<br>&#40;&#60;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Intermediate risk<br>&#40;5&#8211;10&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">High risk<br>&#40;&#62;10&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Clinical signs of right heart failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Absent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Absent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Present&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Symptom progression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Slow&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fast&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Syncope&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Occasional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Frequent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FC-WHO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSmallCaps">I</span>&#44; <span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSmallCaps">III</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSmallCaps">IV</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">6MWT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;440<span class="elsevierStyleHsp" style=""></span>m&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">165&#8211;440<span class="elsevierStyleHsp" style=""></span>m&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;165<span class="elsevierStyleHsp" style=""></span>m&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cardiopulmonary exercise test&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Peak VO<span class="elsevierStyleInf">2</span><br>&#62;15<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;kg<br>&#40;&#62;65&#37;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&#41;<br>VE&#47;VCO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Peak VO<span class="elsevierStyleInf">2</span><br>11&#8211;15<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;kg<br>&#40;35&#8211;65&#37;&#41;<br>VE&#47;VCO<span class="elsevierStyleInf">2</span> 36&#8211;44&#46;99&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Peak VO<span class="elsevierStyleInf">2</span><br>&#60;11<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;kg<br>&#40;&#60;35&#37;&#41;<br>VE&#47;VCO<span class="elsevierStyleInf">2</span> &#62;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">NT-proBNP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">BNP<span class="elsevierStyleHsp" style=""></span>&#60;50<span class="elsevierStyleHsp" style=""></span>ng&#47;L<br>NT-proBNP<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>300<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">BNP 50&#8211;300<span class="elsevierStyleHsp" style=""></span>ng&#47;L<br>NT-proBNP 300&#8211;1400<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">BNP<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>300<span class="elsevierStyleHsp" style=""></span>ng&#47;L<br>NT-proBNP<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>1400<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Echocardiogram or cardiac MRI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RAA<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>18<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleSup">2</span><br>No pericardial effusion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RAA 18&#8211;26<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleSup">2</span><br>Minimal pericardial effusion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RAA<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>26<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleSup">2</span><br>Pericardial effusion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hemodynamic parameters&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RAP<span class="elsevierStyleHsp" style=""></span>&#60;8<span class="elsevierStyleHsp" style=""></span>mmHg<br>CI<span class="elsevierStyleHsp" style=""></span>&#62;2&#46;5<span class="elsevierStyleHsp" style=""></span>L&#47;min&#47;m<span class="elsevierStyleSup">2</span><br>SvO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>65&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RAP 8&#8211;14<span class="elsevierStyleHsp" style=""></span>mmHg<br>CI 2&#8211;2&#46;4<span class="elsevierStyleHsp" style=""></span>L&#47;min&#47;m<span class="elsevierStyleSup">2</span><br>SvO<span class="elsevierStyleInf">2</span> 60&#8211;65&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">RAP<span class="elsevierStyleHsp" style=""></span>&#62;14<span class="elsevierStyleHsp" style=""></span>mmHg<br>CI<span class="elsevierStyleHsp" style=""></span>&#60;2&#46;0<span class="elsevierStyleHsp" style=""></span>L&#47;min&#47;m<span class="elsevierStyleSup">2</span><br>SvO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>60&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">The percentage is related to the reference value for age and sex&#46;</p> <p class="elsevierStyleNotepara" id="npar0020">Modified from Gali&#232; et al&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">3</span></a></p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Risk stratification of patients with pulmonary arterial hypertension&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0025"
        "etiqueta" => "Table 5"
        "tipo" => "MULTIMEDIATABLA"
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        "detalles" => array:1 [
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            "identificador" => "at5"
            "detalle" => "Table "
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        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; SC&#44; subcutaneously&#59; IV&#44; intravenously&#59; kg&#44; kilogram&#59; mg&#44; milligram&#59; ng&#44; nanogram&#59; &#956;g&#44; microgram&#59; h&#44; hour&#59; min&#44; minute&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Drug&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Administration route&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dosage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Adverse Effects&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Epoprostenol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Continuous IV perfusion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#8211;40<span class="elsevierStyleHsp" style=""></span>ng&#47;kg&#47;min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hypotension&#44; flushing&#44; nausea&#47;vomiting&#44; diarrhea&#44; headache&#44; thrombocytopenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Treprostinil&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Continuous IV perfusion<br>Continuous SC perfusion<br><br>Inhaled<br><br>Oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;25&#8211;40<span class="elsevierStyleHsp" style=""></span>ng&#47;kg&#47;min<br><br>6<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;inhalation<br><br>3&#8211;9 inhalations in 4 sessions&#47;day<br><br>0&#46;125&#8211;2&#46;5<span class="elsevierStyleHsp" style=""></span>mg<br>c&#47;12&#8211;8<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Mandibular pain&#44; pain at the injection site&#44; flushing&#44; nausea&#44; vomiting&#44; diarrhea&#44; headache&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Iloprost&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Inhaled&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;5&#8211;5<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;inhalation<br><br>3&#8211;9 inhalations in 4 sessions&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cough&#44; syncope&#44; trismus&#44; flushing&#44; nausea&#44; vomiting&#44; diarrhea&#44; headache&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bosentan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">62&#46;5<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>h in month 1&#59; then 125<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hepatotoxicity&#44; anemia&#44; peripheral edema&#44; angina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ambrisentan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#8211;10<span class="elsevierStyleHsp" style=""></span>mg every 24<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hepatotoxicity&#44; coryza&#44; sinusitis&#44; peripheral edema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Macitentan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10<span class="elsevierStyleHsp" style=""></span>mg every 24<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Anemia&#44; hypotension&#44; peripheral edema&#44; hepatotoxicity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sildenafil&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20<span class="elsevierStyleHsp" style=""></span>mg every 8<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hypotension&#44; amaurosis&#44; hearing loss&#44; priapism&#44; vaso-occlusive crisis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tadalafil&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40<span class="elsevierStyleHsp" style=""></span>mg every 24<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hypotension&#44; amaurosis&#44; hearing loss&#44; priapism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Riociguat&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#8211;2&#46;5<span class="elsevierStyleHsp" style=""></span>mg every 8<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Headaches&#44; gastritis&#44; dizziness&#44; nausea&#44; vomiting&#44; hypotension&#44; anemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Drugs for treating pulmonary arterial hypertension&#46;</p>"
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Review
Update on pulmonary arterial hypertension
Actualización en hipertensión arterial pulmonar
C.R. Mejía Chewa,
Corresponding author
carlos_mejiachew@yahoo.com

Corresponding author.
, S.A. Batresb, J.J. Ríos Blancoa
a Grupo Hipertensión Pulmonar La Paz (GRUHPAZ), Servicio de Medicina Interna, Hospital Universitario La Paz, Madrid, Spain
b Grupo Hipertensión Pulmonar La Paz (GRUHPAZ), Servicio de Neumología, Hospital Universitario La Paz, Madrid, Spain

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