Acute Improved Hemodynamics following Inhaled Iloprost in Chronic Thromboembolic Pulmonary Hypertension

Abstract

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a potential consequence to pulmonary embolism. The histologic picture is similar to idiopathic pulmonary hypertension (IPAH) suggesting that vascular remodeling also contributes to CTEPH. The treatment of choice is pulmonary endarterectomy. However, this treatment option is not adequate for all patients with CTEPH. Currently, no data exist on standard vasodilative therapy for CTEPH. Intravenous and oral prostanoids, both well-known vasodilators in IPAH, have been used with promising results, whereas the same has not been consistently observed for inhaled iloprost. Objective: In this study, we examined acute hemodynamic effects of inhaled iloprost in patients with CTEPH. Methods: In a prospective study, right heart catheterization was performed in 20 patients (mean age 56 years, New York Heart Association class II–IV) at the time of diagnosis of CTEPH. Pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), cardiac output (CO), mean systemic arterial pressure (MAP) and oxygen partial pressure (PaO₂) were obtained before and 20 min after inhaling 5 µg iloprost. Subsequently, all patients were evaluated for pulmonary endarterectomy. Six patients were eligible for surgery. Results: Significant changes in pulmonary and systemic hemodynamics were observed following the inhalation of iloprost (before to after inhalation): PVR: 1,057 ± 404.3 to 821.3 ± 294.3 dyn·s·cm^–5, p < 0.0001; mPAP: 50.55 ± 8.43 to 45.75 ± 8.09 mm Hg, p = 0.0002; CO: 3.66 ± 1.05 to 4.05 ± 0.91 l/min, p < 0.0106. MAP and PaO₂ decreased significantly (MAP: 94.15 ± 11.58 to 89.45 ± 14.29 mm Hg, p = 0.0111; PaO₂: 7.33 ± 1.17 to 6.64 ± 1.25 kPa, p = 0.0260). Conclusions: Hemodynamic changes directly following inhalation of iloprost suggest a significant contribution of a reversible component of vasoconstriction to pulmonary arterial hypertension in patients with CTEPH.

Acute Hemodynamic Effects of Nebulized Iloprost via the I‐Neb Adaptive Aerosol Delivery System in Pulmonary Hypertension

“…16 Despite the nebulizer used, the acute hemodynamic response within the different PH etiologies in our study is comparable to already published data. 8,9,[17][18][19][20] In detail, patients with iPAH, aPAH, or CTEPH who received 10.0 μg of inhaled iloprost showed an increase in exercise capacity and an improvement in symptoms and pulmonary hemodynamics over a 12-week period. 6 Krug et al 9 assessed the acute hemodynamic effects of 5.0 μg inhaled iloprost administered with an ILO-NEB or OPTINEB nebulizer (NEBU-TEC, Elsenfeld, Germany) in 20 patients with CTEPH and found a maximum decrease in PVR of at least 15% with a simultaneous decrease of mPAP and increase of CI.…”

“…Several studies have investigated the safety and efficacy of nebulized iloprost, mostly involving patients with idiopathic PAH (iPAH), inoperable CTEPH, and PAH associated with collagen vascular diseases, and they have reported a significant improvement in hemodynamic parameters, symptoms, and exercise capacity. [6][7][8][9] Since the introduction in 1997 of the first commercial nebulizer, the HaloLite Adaptive Aerosol Delivery (AAD) system, development and research have been performed to improve the design of the nebulizer. The current thirdgeneration I-neb AAD system (Philips Respironics, Parsippany, NJ) is based on a vibrating mesh nebulizer coupled with the AAD technique.…”

Treatment of Chronic Thromboembolic Pulmonary Hypertension: The Role of Medical Therapy and Balloon Pulmonary Angioplasty

“…Of note, 16 of the 20 patients were already receiving one or more PAH-specific medical therapies at the time. 10 Other early studies examining the efficacy of other classes of PH-targeted medical therapy for patient with inoperable CTEPH were similarly limited. Sildenafil, a phosphodiesterase-5 inhibitor, was evaluated in a small, single-center, randomized placebo-controlled trial.…”

Chronic thromboembolic pulmonary hypertension: diagnosis, medical therapy and monitoring

“…PEA öncesi iloprost inhalasyonunun zararlı hemodinamik etkileri olabileceğini bildiren çalışmanın (40) yanı sıra bir başka çalışmada PEA sonrası rezidüel pulmoner hipertansiyon ve bunun hemodinamik etkileri üzerine iloprost inhalasyonunun faydalı etkileri gözlenmiştir (41). Bir başka çalışma inhale iloprostun hemodinamik verilerde akut düzelme sağladığını göstermiş, bunun da KTEPH'da pulmoner hipertansiyon gelişiminde geriye dönebilen vazokonstriksiyon komponentinin varlığını desteklediği ileri sürülmüştür (42). Bir başka küçük çalışmada da inoperabl KTEPH'lu hastalarda subkutan treprostinil infüzyonunun hemodinamik veriler, fonksiyonel kapasite ve sağkalım üzerine iyileştirici etkileri saptanmıştır (43).…”