Chronic Thromboembolic and Pulmonary Arterial Hypertension Share Acute Vasoreactivity Properties: Follow-up of Patients After This Initial Hemodynamic Evaluation

This concept is supported by data indicating that the mechanisms leading to PH in patients who have experienced repeated pulmonary thromboembolic events are not only mechanistic (ie, nonrecanalized thrombotic vessel occlusion), but possibly also are related to vascular remodeling that is located distal to the occluded ar-tery and in noninvolved adjacent pulmonary vessels, possibly leading to endothelial dysfunction. The vascular lesions in these noninvolved vessel segments were histologically indistinguishable from those in PAH patients. In line with this concept are observations that almost half of the patients with CTEPH did not have a history suggestive of acute pulmonary thromboembolism and that only 45% of patients have findings that are suggestive of previous venous thrombosis on lower extremity duplex ultrasound. In addition, the incidence of hereditary thrombophilia seems not to be increased in patients with CTEPH. Central pulmonary artery thrombi have been shown to occur also in patients with PAH.

In line with the results of studies reporting an active vascular remodeling process in CTEPH patients are also studies reporting the successful use of oral and inhaled vasodilators in patients with CTEPH. Thus, our results indicating a similar acute vasodilator response in patients with CTEPH and PAH support this new concept and encourage future vasodilator trials also in selected patients with CTEPH who are waiting for thrombendarterectomy, or who are not operable, or who have a major contraindication for surgery, many of whom were experiencing a very restricted quality of life with dismal prognosis. generic wellbutrin

The primary objective of acute vasodilator testing in patients with PAH is to identify the subset of patients who might be treated effectively with oral calcium-channel blockers. However, this drug class will probably never be a valuable therapeutic option in patients with CTEPH due to its capacity to increase ventilation-perfusion mismatch and thus intrapulmonary shunt-ing.’ In patients with PAH, a pronounced response to short-acting pulmonary vasodilators has been shown to be associated with a better prognosis, at least in some patients. However, vasoreactivity testing has not been recommended for the assessment of long-term prognosis because of great interindividual variability. This view might be strengthened by our study results, which failed to show an association between acute vasodilatation response and change in functional class or 6MWD 3 and 12 months after the initiation of long-term vasodilator therapy in both CTEPH and PAH patients. Our findings also indicate that neither a structural difference between CTEPH and PAH nor the baseline vasodilator reserve are indicators of long-term treatment response. Thus, there is no rationale for performing vasoreactivity testing at the baseline evaluation in CTEPH patients as well. But these findings have to be interpreted with caution, as the present study was not designed to answer question concerning the relationship between acute vasoreactiv-ity and the long-term response to vasodilatative treatment, as individual treatment strategies after the acute assessment differed considerably, not allowing a formal correlation study. Further, the results of the present study have to be interpreted with caution, as, for logistical reasons, the design was not randomized placebo-controlled, and investigators were not blinded concerning the patient’s medical records and history. This study, however, provides a rationale for future studies that would be sufficiently powered and designed to answer these clinically important questions.
In summary, in the present study we could show that, despite obvious differences between CTEPH and PAH, both entities share similar acute vasoreactivity properties and vessel compliance, indicating some common pathogenetic pathways, thus also providing a rationale for long-term vasodilator and antiproliferative treatment strategies in patients with inoperable CTEPH.

This entry was posted in Respiratory Symptoms and tagged chronic thromboembolic pulmonary hypertension, pulmonary arterial hypertension, pulmonary hemodynamics, pulmonary vascular compliance, vasoreactivity testing.