Pulmonary Hypertension Associated with Heart Failure with Preserved Ejection Fraction: Acute Hemodynamic Effects of Inhaled Iloprost

Abstract

Iloprost, an inhaled synthetic prostacyclin analogue, improves hemodynamic and clinical status with minimal systemic adversity in patients with pulmonary arterial hypertension. Our single-site, prospective case series aimed to determine the effects of iloprost in subjects with group 2 pulmonary hypertension and heart failure with preserved ejection fraction. Patients referred to Boston Medical Center for initial evaluation of suspected pulmonary hypertension received a test dose of 2.5 μg inhaled iloprost, followed by two subsequent doses of 5 μg. Hemodynamic measurements were recorded for each inhalation after 15, 30, 60, and 90 minutes. Results were analyzed via paired t test and signed-rank test. Eight subjects fulfilled criteria and elected to enter the study. There was a reduction of pulmonary arterial pressure (by an average of 7.0 mmHg [P ¼ 0.005] and 4.7 mmHg [P ¼ 0.021] with the first and second 5-μg inhalations, respectively) and pulmonary vascular resistance (by an average of 161.9 dyn·s/cm 5 [P ¼ 0.019] and 95.0 dyn·s/cm 5 [P ¼ 0.014] with the first and second 5-μg inhalations, respectively). There were trends for increased cardiac output and decreased oxygen saturation. There were no changes in other vital or hemodynamic parameters, including pulmonary capillary wedge pressure. All patients completed each cycle of iloprost administration without preestablished termination criteria. In patients with pulmonary hypertension and heart failure with preserved ejection fraction, inhaled iloprost resulted in acute reduction of pulmonary arterial pressure and pulmonary vascular resistance. Further evaluation of iloprost in this subset of patients is warranted.

Right heart dysfunction and failure in heart failure with preserved ejection fraction: mechanisms and management. Position statement on behalf of the Heart Failure Association of the European Society of Cardiology

“…Chronic intravenous epoprostenol is associated with increased risk of mortality in patients with HFrEF, although the exact mechanisms are unclear . In a small pilot study in patients with PH‐HFpEF, acute inhalation of iloprost resulted in a significant reduction in PA pressure and PVR after 15 minutes . No data regarding the effects of iloprost on RV performance in HFpEF are currently available.…”

Therapeutic approaches in heart failure with preserved ejection fraction: past, present, and future

“…Currently, therapy with sGC stimulators and activators is further studied in various trials (NCT03153111, NCT03254485, NCT02744339, and NCT03547583). The RCT VITALITY-HFpEF (NCT03547583) for instance, will primarily evaluate treatment effects of vericiguat regarding physical function [9] and Böhm et al [135] assessed by the KCCQ PLS (Kansas City Cardiomyopathy Questionnaire Physical limitation score).…”

Effect of iloprost inhalation on postoperative outcome in high-risk cardiac surgical patients: a prospective randomized-controlled multicentre trial (ILOCARD)

“…33 Nevertheless, pulmonary capillary wedge pressures in our study patients were not indicative for such a counterproductive mechanism, a finding recently reported also in medical patients with PH due to left heart failure. 34 Fifth, although focusing on a high-risk population, the inclusion and exclusion criteria may have been too liberal (resulting in only 60% of the included patients suffering from PH and having a NYHA class C III). Notably, Sixth, unbalanced pulmonary vasoconstriction is only one pathophysiologic mechanism contributing to post-ECC cardiopulmonary dysfunction.…”

“…Iloprost 116 13 [10][11][12][13][14][15][16][17] 124 11 [8][9][10][11][12][13][14][15] 124 14 [10][11][12][13][14][15][16][17] 123 13 [10][11][12][13][14][15][16] 120 13 [10][11][12][13][14][15][16][17] MPAP (mmHg) Placebo 106 28 [22][23][24][25][26][27][28][29][30][31][32][33][34]…”

“…Iloprost 110 29 [24][25][26][27][28][29][30][31][32][33][34][35][36][37] 119 26 [20][21][22][23][24][25][26][27][28][29][30][31][32] 121 27 [22][23][24][25][26][27][28][29][30][31][32] 121 30 [25][26][27][28][29][30][31][32][33][34] 114 30 [25][26][27][28]…”