Background
Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening disease manifested by progressive pulmonary vascular remodeling, compromised pulmonary blood flow and right heart failure. Most studies explore how pulmonary endothelial function modulates disease pathogenesis. We hypothesize that IPAH is a progressive panvasculopathy, affecting both pulmonary and systemic vascular beds, and that systemic endothelial dysfunction correlates with disease severity. Recent studies demonstrate systemic endothelial dysfunction in adults with pulmonary hypertension, however adults often have additional comorbidities affecting endothelial function. Systemic endothelial function has not been explored in children with IPAH.
Methods
This single-center, prospective, cross-sectional study examined brachial artery flow mediated dilation (FMD), a nitric oxide mediated, endothelial-dependent response, in children with IPAH and matched controls. FMD measurements were compared with clinical and echocardiographic measures of IPAH severity.
Results
Thirteen patients and 13 controls were studied, ages 6–20 years old. FMD was decreased in IPAH subjects compared with controls (5.1 +/− 2.1% vs 9.7 +/− 2.0%; p<0.0001). In IPAH subjects, FMD correlated directly with cardiac index (R2=0.34, p=0.035), and inversely with tricuspid regurgitation velocity (R2=0.57, p=0.019) and right ventricular myocardial performance index (R2= 0.44, p=0.028).
Conclusions
The presence of systemic endothelial dysfunction in children with IPAH and its strong association with IPAH severity demonstrate that IPAH is a global vasculopathy. Although morbidity in IPAH is typically associated with pulmonary vascular disease, systemic vascular changes may also relate to disease pathogenesis and progression. Further study into shared mechanisms of systemic and pulmonary endothelial dysfunction may contribute to future therapies for IPAH.
Two unique cases are presented of infants with signs of vein of Galen malformations, whose unsuspected associated sinus venosus atrial septal defects were detected during routine echocardiography. A conservative approach to cardiac treatment is advocated.
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