ACUTE AND PROLONGED EFFECT OF NEW TREATMENTS (LEVOSIMENDAN AND SACUBITRIL/VALSARTAN) IN HEART FAILURE: AN HOLISTIC EVALUATION
Creators: name: SPADAFORA, EMANUELE
Publisher: name: Universit� degli Studi di Milano
Year: 2019

description: Alveolar-capillary membrane evaluated by carbon monoxide diffusion (DLCO) plays an important role in heart failure (HF). Surfactant Proteins (SPs) have also been suggested as a worthwhile marker. In acute HF, Levosimendan improves pulmonary hemodynamics and reduces lung fluids but associated SPs and DLCO changes are unknown. Sixty-five acute HF patients underwent spirometry, cardiopulmonary exercise test (CPET) and SPs determination before and after Levosimendan. Levosimendan caused natriuretic peptide-B (BNP) reduction, peakVO2 increase and VE/VCO2 slope reduction. Spirometry improved but DLCO did not. SP-A, SP-D and immature SP-B reduced (73.7?�?25.3 vs. 66.3?�?22.7?ng/mL*, 247?�?121 vs. 223?�?110?ng/mL*, 39.4?�?18.7 vs. 34.4?�?17.9AU*, respectively); while mature SP-B increased (424?�?218 vs. 461?�?243?ng/mL, *?=?p?&lt;?0.001). Spirometry, BNP and CPET changes suggest hemodynamic improvement and lung fluid reduction. SP-A, SP-D and immature SP-B reduction indicates a reduction of inflammatory stress; conversely mature SP-B increase suggests alveolar cell function restoration. In conclusion, acute lung fluid reduction is associated with SPs but not DLCO changes. SPs are fast responders to alveolar-capillary membrane condition changes. On the other hand, regarding chronic heart failure, Sacubitril/Valsartan represents a novel therapy in the treatment of chronic heart failure with reduced ejection fraction (HFrEF), has recently proved efficacy in improving exercise tolerance and cardiac performance. We enrolled a cohort of HFrEF outpatients eligible for sacubitril/valsartan and performed serial cardiopulmonary exercise tests (CPET), pulmonary function tests, laboratory and echocardiographic assessments before and during the gradual titration of this treatment, in order to evaluate its effects on cardiopulmonary function and left ventricular remodeling. In this interim analysis, we examined twenty-five patients treated with sacubitril/valsartan for at three months. At a mean follow-up of 169�74 days, 92% of patients reached the maximum dose, without important safety concerns. Ejection fraction increased (31.0�5.4 vs. 37.2�9.6 %; p=0.009), while left ventricular end-diastolic and end-systolic volumes decreased (respectively, 116.8�31.4 vs. 90.5�21.3 ml, p=0.011; 80.9�24.5 vs. 58.2�21.4 ml, p=0.004). Peak oxygen consumption (VO2) improved from 63.4�12.5 to 70.3�13.3 % of predicted (p=0.002), along with workload at maximal exercise (97.0�39.3 vs. 103.7�39.7 watt, p=0.001) and VO2 at the anaerobic threshold (881�278 to 1056�350 ml, p=0.012). Minute ventilation/carbon dioxide production relationship (VE/VCO2 slope) did not reach statistical significance in this sub-population. New York Heart Association functional class improved (p=0.004), together with a significant decrease of MECKI (Metabolic Exercise test data combined with Cardiac and Kidney Indexes) score from 3.0 (IQR 1.7-6.3) to 1.8 (0.8-3.6) %, with a positive impact on two-year HF prognosis (p=0.009).In conclusion medium-term treatment with sacubitril/valsartan demonstrated beneficial effects on exercise tolerance, left ventricular remodelling and functional status, confirming the results from previous clinical trials in real-life. The longer follow-up and larger population of the finished study will further contribute to the assessment of its positive effects on HF patients.