@Article{chd.12688,
AUTHOR = {Mariana M. Clavé, Nair Y. Maeda, Ana M. Thomaz, Sergio P. Bydlowski, Antonio A. Lopes},
TITLE = {Phosphodiesterase type 5 inhibitors improve microvascular dysfunction markers in pulmonary arterial hypertension associated with congenital heart disease},
JOURNAL = {Structural and Congenital Heart Disease},
VOLUME = {14},
YEAR = {2019},
NUMBER = {2},
PAGES = {246--255},
URL = {http://www.techscience.com/schd/v14n2/38758},
ISSN = {3071-1738},
ABSTRACT = {<b>Background:</b> Ideally, vasodilator therapies for pulmonary arterial hypertension (PAH) should 
have a favorable impact on markers of vascular dysfunction, in addition to their known effects 
on hemodynamics, cardiac function, and patient’s physical capacity.<br/>
<b>Methods:</b> We analyzed circulating (plasma) markers of endothelial and platelet activation/dys‐
function (enzyme‐linked immunoassays) in the specific setting of advanced PAH associated 
with congenital heart disease, during the course of sildenafil and tadalafil therapies. Thirty‐one 
patients were enrolled (age 10‐54 years), most of them with chronic hypoxemia and elevated 
hematocrit. Drugs were administered orally for 6 months (sildenafil [n = 16], 20 mg t.i.d.; tada‐
lafil [n = 15], single daily dose of 40 mg). Measurements were performed at baseline, and 90 
and 180 days.<br/>
<b>Results:</b> Compared to controls, patients had elevated baseline β‐thromboglobulin (β‐TG, 
P = .002), P‐selectin (P = .027), tissue‐type plasminogen activator (t‐PA, P = .009), and von 
Willebrand factor antigen (VWF:Ag, P = .010). Thrombomodulin was importantly reduced (TM, 
P < .001), while soluble CD40 Ligand was not changed (P = .320). Tadalafil administration was 
associated with improvement of β‐TG (P = .004), t‐PA (P = .003) and TM (P = .046) levels, while 
P‐selectin was improved by sildenafil treatment only (P = .034). VWF:Ag improved transiently 
in the sildenafil group (P = .019). Both therapies were associated with improvement of the 
physical capacity (functional class and distance walked during the 6‐minute test, P < .05), he‐
matocrit and hemoglobin level (P < .05), and health‐related quality of life (physical and mental 
components, P < .05).<br/>
<b>Conclusion:</b> In PAH associated with congenital heart disease, phosphodiesterase 5 inhibitors 
seem to have beneficial actions at microcirculatory level, beyond the proposed effects as 
vasodilators.},
DOI = {10.1111/chd.12688}
}