Abnormal Pulmonary Artery Stiffness in Pulmonary Arterial Hypertension: In Vivo Study with Intravascular Ultrasound

Background: There is increasing recognition that pulmonary artery stiffness is an important determinant of right ventricular (RV) afterload in pulmonary arterial hypertension (PAH). We used intravascular ultrasound (IVUS) to evaluate the mechanical properties of the elastic pulmonary arteries (PA) in subjects with PAH, and assessed the effects of PAH-specific therapy on indices of arterial stiffness. Method: Using IVUS and simultaneous right heart catheterisation, 20 pulmonary segments in 8 PAH subjects and 12 pulmonary segments in 8 controls were studied to determine their compliance, distensibility, elastic modulus and stiffness index beta. PAH subjects underwent repeat IVUS examinations after 6-months of bosentan therapy. Results: At baseline, PAH subjects demonstrated greater stiffness in all measured indices compared to controls: compliance (1.50 +/- 0.11 x 10(-2) mm(2)/mmHg vs 4.49 +/- 0.43 x 10(-2) mm(2)/mmHg, p<0.0001), distensibility (0.32 +/- 0.03%/mmHg vs 1.18 +/- 0.13%/mmHg, p<0.0001), elastic modulus (720 +/- 64 mmHg vs 198 +/- 19 mmHg, p<0.0001), and stiffness index b (15.0 +/- 1.4 vs 11.0 +/- 0.7, p = 0.046). Strong inverse exponential associations existed between mean pulmonary artery pressure and compliance (r(2) = 0.82, p<0.0001), and also between mean PAP and distensibility (r(2) = 0.79, p = 0.002). Bosentan therapy, for 6-months, was not associated with any significant changes in all indices of PA stiffness. Conclusion: Increased stiffness occurs in the proximal elastic PA in patients with PAH and contributes to the pathogenesis RV failure. Bosentan therapy may not be effective at improving PA stiffness.