The Application Of Intravascular Ultrasound To Evaluate Pulmonary Vascular Properties And Mortality In Patients With Pulmonary Arterial Hypertension

BackgroundPulmonary arterial hypertension(PAH) is a progressive disease of the pulmonary vasculature leading to increased pulmonary vascular resistance(PVR), elevated pulmonary artery pressure(PAP), right ventricular dysfunction, and ultimately, right ventricular failure and death.The pathologic changes in patients with PAH are characterized by intimal proliferative, medial hypertrophic, and fibrotic changes; adventitial thickening with moderate perivascular inflammatory infiltrates; and plexiform and thrombotic lesions. These changes may induce the increase of PVR and PAP accompanied by the abnormalities in pulmonary vascular properties(PVPs) and eventually leads to right-heart failure.PAH associated with connective tissue disease(PAH-CTD) has the high mortality and is frequently complicated to be the main cause of death in connective tissue disease. Right Heart Catheterization is considered to be the gold standard method in diagnosing and evaluating PAH. However, it fails to detect PVPs and to differentiate very small changes in PVPs between different types of PAH. Let alone the prognosis influenced by different vascular remolding in different segment. ObjectiveWe aimed to explore the application of intravascular ultrasound(IVUS) to evaluate pulmonary vascular properties(PVPs) and mortality in patients with pulmonary arterial hypertension, including patients with PAH-CTD. MethodsConsecutive patients(n = 51) with systolic pulmonary artery pressures(SPAPs) ≧ 40 mm Hg on echocardiography were prospectively enrolled in the study and underwent RHC and IVUS between July 2011 and March 2014. After underwent RHC, they were divided into 3 groups: PAH associated with connective tissue diseases(PAH-CTDs)(group1, n=25), PAH due to other causes(group2, n=15), and CTDs patients without pulmonary hypertension(PH)(group3, n=11). And each detected pulmonary vessel was subdivided into two segments based on IVUS, a distal segment with a VD <5mm and a proximal segment >5mm. Furthermore, PAH groups(groups1 and 2) were classified as distal remodeling subtype group(n=22) when the percentage of mean wall thickness(WTP) of the pulmonary distal segment was higher than that of the proximal segment, otherwise, they were classified as proximal remodeling subtype group(n=18). All patients were followed-up to compare the differences among clinical variables, hemodynamic values, PVPs and survival rates. ResultsA total of 408 segments of pulmonary arteries were studied. PAH groups(group1 and group 2) demonstrated a greater mean wall thickness(MWT) than group3(0.30±0.02 and 0.33±0.02 vs. 0.21±0.02 mm, all P<0.01), and a higher WTP as well(13.6±0.6 and 14.4±0.8 vs. 9.6±1.0%, all P<0.01). Pulmonary vascular mechanical properties(PVMPs) including compliance(8.9±0.8×10-2 and 6.3±0.7×10-2 vs. 41.6±5.0×10-2mm2/mm Hg, all P<0.01), distensibility(0.8±0.1 and 0.6±01 vs. 3.2±0.4%/mm Hg, all P<0.01), elastic modulus(169.3±15.1 and 253.0±22.1 vs. 43.8±4.3mm Hg, all P<0.01) and stiffness index β(4.2±0.4 and 5.2±0.3 vs. 2.4±0.3, all P<0.05) were found to be worse in PAH groups than group3. PVMPs in in group1 was be better than in group2 for EM(169.3±15.1 vs 253.0±22.1mm Hg,P<0.01), although the compliance(P=0.07), distensibility(P=0.06) and the stiffness index β(P=0.12) were not stastically different between two groups.An inverse exponential association was found between PVMPs and hemodynamic abnormalities: SPAP and compliance(R2=0.7, P<0.001), SPAP and distensibility(R2=0.8, P<0.001), SPAP and EM(R2=0.7, P<0.001), m PAP and compliance(R2=0.7, P<0.001), m PAP and distensibility(R2=0.7, P<0.001), m PAP and EM(R2=0.6, P<0.001), PVR and compliance(R2=0.6, P<0.001), PVR and distensibility(R2=0.6, P<0.001), and PVR and EM(R2=0.5, P<0.001). The percentage of CD3+ T cells was higher in group1 than group2(73.5±3.1 vs. 61.1±0.7%, P<0.01). There were significant decreased values compared with baseline for ET-1, TGF-β1 and PF-4 in 20 PAH –CTD patients after PAH-targeted therapy.Among PAH groups, there was no difference between group 1 and group 2 in survival curve(12% vs 13%, P >.05),but the distal remodeling subtype had a higher mortality than proximal remodeling subtype(23% vs. 0%, P<0.05). ConclusionsIVUS is useful in assessment of PAH by evaluating pulmonary vascular properties and mortality. PAH patients have worse PVPs than those with normal pulmonary pressure. PAH-CTD patients have better PVPs than other PAH patients. Autoimmunity may be an important role in the development of CTD-PAH. Early intervention may improve the hemodynamics and pulmonary vascular proterties. The survival rate is similar between PAH-CTD and other PAH group, while the distal remolding subtype has the higher mortality than the proximal remolding subtype in PAH. The classification of proximal and distal remodeling subtype of PAH may be proposed to predict mortality and evaluate prognosis of PAH patients on clinical practice.