Assessment of Recovery of Functional Capillary Surface Area in Patients Undergoing a Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension

Chronic thromboembolic pulmonary hypertension [CTEPH] affects approximately 3% of patients with a prior pulmonary embolism. In CTEPH patients, the acute pulmonary emboli do not resolve but instead become organized in the pulmonary artery walls causing physical luminal obstruction and impeding forward blood flow. Pulmonary vascular resistance rises, and right heart failure can ultimately develop. Currently, there are 3 therapeutic options for treating CTEPH: 1) pulmonary thromboendarterectomy involving surgical removal of the clots; 2) balloon pulmonary angioplasty involving opening of the narrow areas using angioplasty balloons; 3) medical therapy for distal disease using the soluble guanylate cyclase stimulator riociguat.

Balloon pulmonary angioplasty (BPA), depending on the number of narrow pulmonary artery segments that are opened, can provide immediate hemodynamic benefit in appropriate patients. Although the hemodynamics usually do not completely normalize after a single BPA session, cardiac output may increase and mean pulmonary artery pressure may fall. It is unclear how much pulmonary microvasculature must be restored to obtain this benefit, both in terms of number of segments, and in terms of the amount of downstream pulmonary microvasculature that must be regained.

The investigators have developed a technique in humans that assesses functional capillary surface area (FCSA). It involves measuring the metabolism of injected trace quantities of 3H-benzoyl Phe-Ala-Pro (BPAP), as the peptide passes through the lung circulation, and interacts with the capillary endothelial surface area. The investigators have established the range of normal in humans, studied the effects of exercise, and explored the reduction in FCSA in disease, including various types of pulmonary hypertension. Most germane to the present study, our previous work (Orfanos et al J Throm Hemostas 2008) demonstrated that the downstream capillary bed in CTEPH is functionally normal but FCSA is reduced because of upstream arteriolar blockage by organized thrombi. The average FCSA in untreated CTEPH is decreased by approximately 50%. Some of this FCSA should be immediately available to accept blood flow (recruitment) once the corresponding upstream segmental pulmonary artery is reopened by BPA.

Hypotheses:

1. The measured FCSA will immediately increase in CTEPH patients after BPA.
2. The amount of FCSA regained (recruited) will be proportional to the number of pulmonary arterial segments dilated.
3. The decrease in mean pulmonary arterial pressure towards normal may be a better indicator of FCSA regained than will be reduction in pulmonary vascular resistance.