Acute Pulmonary Vasodilator Testing and Long-Term Clinical Course in Segmental Pulmonary Vascular Disease

Abstract

Results of acute pulmonary vasodilator testing (AVT) and the outcome of medical therapy have not been described in patients with segmental pulmonary vascular disease (SPVD). We sought to compare the pulmonary vasodilatory effects of oxygen, oxygen with nitric oxide, and diltiazem, and to describe the clinical course of patients with SPVD and pulmonary hypertension. A retrospective review of 16 patients with pulmonary hypertension and SPVD involving 2-3 major lung segments who underwent AVT between January 2000 and December 2015 was performed. Baseline hemodynamic measurements were obtained with patients breathing ≤ 30% oxygen. AVT was performed using 100% oxygen, 100% oxygen with 20 ppm nitric oxide, 21-35% oxygen, and 21-35% oxygen with intravenous diltiazem. The events associated with their long-term care were described. Nine of 16 patients were acutely responsive during AVT using the Sitbon criteria. The change in mean pulmonary artery pressure with oxygen or oxygen with nitric oxide (19 ± 12 mmHg) was significantly greater than the change with diltiazem (7 ± 5 mmHg). Pulmonary vasodilator therapy was initiated or escalated after AVT in 12 patients. Five patients subsequently experienced a decrease in mean pulmonary artery pressure or normalization in B-type natriuretic peptide. Three patients experienced adverse events associated with therapy. The actuarial survival was 94% over a period of 1-20 years. This study suggests that AVT can be used to identify patients with SPVD who are reactive to oxygen, oxygen with nitric oxide, and diltiazem. Clinical improvement was temporally associated with pulmonary vasodilator therapy in some patients with few adverse effects.

Intervening with the Nitric Oxide Pathway to Alleviate Pulmonary Hypertension in Pulmonary Vein Stenosis

“…Together with the observations that eNOS inhibition produced a larger increase in tPVRi in PVB as compared to sham, and the relatively modest vasodilation induced by SNP as compared to PDE5 inhibition, this suggests that the NO pathway is hyperactive in PVB pulmonary vasculature, probably as a compensatory mechanism, and that adding additional NO has a very limited effect. These data are consistent with the study of Domingo et al, which showed that NO on top of 100% oxygen did not induce further pulmonary vasodilation [25]. Interestingly, eNOS expression was higher in HP/HF as compared to HP/LF, and tended to be higher compared to the corresponding lung lobe of sham animals.…”

“…Most patients with PVS [25], as well as swine with PVS [15], show a decrease in pulmonary artery pressure upon vasoreactivity testing with inhaled 100% oxygen. In our previous study, we showed that ET A/B blockade with tezosentan resulted in a decrease in tPVRi in swine with PVB, and that this vasodilator effect increased over time [17].…”

Management of Pediatric Pulmonary Vein Stenosis

“…47 Although historically controversial, there is growing evidence suggesting not only the safety of pulmonary vasodilators in the setting of PVS but also efficacy and utility in patients with severe PVS. 47,50,65 Any use of standard pulmonary vasodilators in this population should be done so with due caution and carefully planned reevaluation to determine the efficacy or progression of PVS. Pulmonary vasodilators are never indicated with diffuse, symmetrical PVS, similar to the contraindication with the pulmonary veno-occlusive disease.…”

Pulmonary Vein Stenosis in Children: A Programmatic Approach Employing Primary and Anatomic Therapy

“…Catheterization allows for vasoreactivity testing in patients with PVS and pulmonary artery hypertension (PAH). Our center has been more aggressive about using pulmonary vasodilator therapy for patients with elevated PA pressures who have undergone such vasoreactivity assessment [17]. In recent years, patients with RV pressures > 50% systemic at catheterization are given a trial with pulmonary vasodilators while they are in the hospital.…”