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Background Sacubitril/valsartan is a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI) recommended in the guidelines to reduce morbidity and mortality in patients with symptomatic heart failure (HF) with reduced ejection fraction (HFrEF). Although the recent widespread use of the drug, data on left ventricle (LV) reverse remodeling and improvement in functional capacity (FC) under treatment are still lacking. Case presentation A 73 years old man with a known HFrEF was admitted to the hospital for clinical review due to progressive worsening dyspnea in the last 6 months (NYHA class III) with high NTproBNP values. Echocardiography showed dilated LV (EDVi/ESVi 137/98 ml/m2) with severe reduction in ejection fraction (EF), moderate/severe aortic incompetence, moderate functional mitral regurgitation. A maximal, ramp-protocol, cardiopulmonary exercise test (CPET) showed a moderate reduction in FC with signs of cardiogenic limitation. He was started on Sacubitril/Valsartan 24/26mg b.i.d. with progressive up-titration of the dose until a maximum dose of 97/103mg b.i.d. and without any other change in the therapy. ARNI was well tolerated without hypotension, worsening renal function or hyperkaliemia. After 3 months the echocardiography showed a reduction in LV volumes (EDVi/ESVi 112/72 ml/m2) with mild improvement in EF (from 28% to 34%) and increased FC, leading to a 56% reduction in estimated HF mortality at 2 years assessed through MECKI Score (See tab. 1 and Fig. 1). NTproBNP value was also reduced compared to baseline. Conclusion We present a case of a short term improvement in LV and atrium volumes and FC after 3 months of treatment with Sacubitril/valsartan in a patient with HFrEF. More studies are needed to assess LV volumes and CPET values response to ARNI. Tab.1 Basaline 3 months Δ NYHA Class II III - MECKI Score (%) 5.12 2.23 -56-4% Peak VO2 /% of predicted) 60 72 +20% Maximal Work (W) 68 83 +22.1% Mitral regurgitation ++ + - eGFR (ml/min/1,73m2) 64 65 +1.6% Potassium (mmol/L) 4.26 4.20 -1.4% Aortic regurgitation +++ ++ - Clinical changes after the 3 months follow-up Abstract P638 Figure. Fig. 1

P638 Short term reverse remodeling and exercise capacity improvement in a patient with valvular heart failure treated with Sacubitril Valsartan