Comparison of levosimendan, NO, and inhaled iloprost for pulmonary hypertension reversibility assessment in heart transplant candidates

Abstract

Aims Assessing reversibility of pulmonary vascular changes through vasoreactivity testing (VRT) optimizes end-stage heart failure patient selection for heart transplant. All efforts should be made to unload the left ventricle and reduce pulmonary vascular resistance to effectively exclude irreversible pulmonary hypertension. Methods and results We reviewed our centre's cardiac transplant registry database (2009-2017) for VRT and compared haemodynamic responses with 40 ppm inhaled NO (n = 14), 14-17 μg inhaled iloprost (n = 7), and 24 h 0.1 μg/kg/min intravenous levosimendan (n = 14). Response to levosimendan was assessed by repeat right heart catheterization within 72 h. Baseline clinical and haemodynamic features were similar between groups. VRT was well tolerated in all patients. All drugs effectively reduced pulmonary artery pressures and transpulmonary gradient while increasing cardiac index, although levosimendan had a greater impact on cardiac index increase (P = 0.036). Levosimendan was the only drug that reduced pulmonary artery wedge pressure (P = 0.004) and central venous pressures (P < 0.001) and increased both left and right ventricular stroke work indexes (P = 0.020 and P = 0.042, respectively) and cardiac power index (P < 0.001) compared with NO and iloprost. Right ventricular end-diastolic pressures and central venous pressure were only decreased by levosimendan. The rate of positive responses (≥10 mmHg decrease or final mean pulmonary artery pressure ≤40 mmHg with increased/unaltered cardiac index) was lower with inhaled iloprost (14%) than with either levosimendan or NO (71% and 64%, respectively; P < 0.05). Conclusions Levosimendan may be a safe and effective alternative for pulmonary hypertension reversibility assessment or a valuable pre-test medical optimization tool in end-stage heart failure patient assessment for heart transplantation offering extended haemodynamic benefits. Whether it increases the rate of positive responses or allows a better selection of candidates to heart transplantation remains to be established.

Levosimendan in intensive care and emergency medicine: literature update and expert recommendations for optimal efficacy and safety

“…Based on data from a retrospective review of a single-centre transplant list, Tavares-Silva and colleagues [ 95 ] deemed levosimendan to be a safe and effective alternative to either iloprost or nitric oxide for PH reversibility assessment of heart transplant candidates but emphasized that their data offered no insights into whether the use of levosimendan in this way facilitated better selection of transplant candidates or was associated with any robust indication of improved outcomes from transplantation. Levosimendan was the only drug of the three reviewed that reduced pulmonary artery wedge pressure and CVP.…”

Advances in the Study of Inhaled Formulations for the Treatment of Pulmonary Arterial Hypertension

“…Iloprost is a synthetic and relatively stable cyclin analogue with a relatively short duration of action, administered by inhalation 6-9 times a day. It has been demonstrated that the use of 100 μ g of iloprost in 6-9 inhalations per day for varying lengths of time, up to 1 year, in patients with different grades of PAH has been found to provide short- or long-term benefits [ 19 ]. Currently, the United States, Australia, and some other European countries have approved inhaled iloprost for direct use in the treatment of WHO cardiac class III or IV PAH, and in China, it was approved for the treatment of moderate PAH in 2006.…”

Hemodynamic Changes After Left Ventricular Assist Device Implantation Among Heart Failure Patients With and Without Elevated Pulmonary Vascular Resistance

“…This mechanism is often demonstrated in invasive hemodynamic studies testing PVR reactivity among HT candidates. A positive response can be defined based on reduction of pulmonary pressure and PCWP with concomitant increase in CO ( 18 ). Nevertheless, changes in CO were not included in most previous studies evaluating LVAD therapy in elevated PVR patients ( 13 – 17 ).…”