1406Inhaled iloprost, exercise hemodynamics, and ventricular performance in heart failure with preserved ejection fraction

Abstract

Background A dramatic increase in pulmonary capillary wedge pressure (PCWP) during exercise is observed in patients with heart failure with preserved ejection fraction (HFpEF). The prostacyclin pathway is involved in pulmonary hypertension and iloprost is a prostacyclin analogue. The acute onset vasodilator effect of inhaled iloprost makes it a good candidate to decrease exercise-induced PCWP. This study determined whether iloprost inhalation could improve exercise hemodynamics and cardiac reserve in HFpEF. Methods Thirty-four HFpEF subjects were enrolled in this double-blind, randomized, placebo-controlled, parallel-group trial. Subjects received invasive cardiac catheterization and underwent expired gas analysis at rest and during exercise, before and 15 minutes after treatment with either inhaled iloprost or placebo. Results At baseline, enrolled subjects showed an increase in PCWP during exercise (PCWP = 16 (14–23) mmHg to 27 (21–36) mmHg; p<0.0001). After drug inhalation treatment, the primary endpoint was achieved whereby exercise PCWP was significantly reduced by iloprost compared to placebo (adjusted mean: 20 (16–29) mmHg vs. 23 (17–32) mmHg; p=0.002). Iloprost showed a trend for better cardiac output reserve with exercise (0.2 (−1.3 to 1.2) L/min vs. −0.7 (−1.9 to 0.1) L/min; p=0.099) and normalized the increase in cardiac output relative to oxygen consumption. Iloprost improved the pulmonary artery pressure flow relationships in HFpEF and showed a trend for increased left ventricular stroke work with exercise compared to placebo, indicating an improvement in ventricular performance with stress. Table shows exercise baseline-corrected values (exercise values after receiving study drug minus exercise values prior to study drug) Placebo (n=17) Iloprost (n=17) p Value PA systolic, mmHg 0 (−4 to 6) −11 (−23 to −5) <0.0001 PCWP, mmHg −2 (−3 to 2) −7 (−12 to −5) <0.0001 PVR, mmHg/l/min 0 (−0.5 to 0.3) −0.1 (−0.5 to 0.4) 0.9 SVR, DSC 102 (16 to 188) 5 (−162 to 108) 0.057 LVSW, g/beat −3 (−30 to 6) 7 (−13 to 20) 0.079 CO, l/min −0.7 (−1.9 to 0.1) 0.2 (−1.3 to 1.2) 0.099 Stroke volume, ml −8 (−24 to 1) 0 (−19 to 10) 0.3 Values are median (interquartile range). Conclusions Iloprost inhalation improved hemodynamic deficit during exercise in patients with HFpEF. Prospective trials testing long-term iloprost therapy in this population are warranted.