Eligibility criteria were expanded. Eligible patients should be older than 45 years (instead of 18) to avoid inclusion of possible pregnant women. Exclusion criteria list was expanded. Therapy schema was modified for a better overview

Primary endpoint “Count of the hospitalization’s days after 60 days” was classified as secondary endpoint. The secondary endpoint “Mortality or Hospitalizations after 180 days” is now the primary endpoint of the study. Study population was increased from 351 patients per group to 385 patients per group. Third tone would be assess using a special holter device (Audicor) during the first 24 hours. At the beginning of the hospitalization and before discharge, lower limbs circumference and central venous pressure will be measured, the latest not invasively using an ultrasound device. At admission, at 48 hours and before discharge, subjective dyspnea assessment will be carried

The primary endpoint “mortality or hospitalizations after 180 days” was changed to “mortality or rehospitalizations due to heart failure after 180 days”. No sample size adjustment. New study centers were included to the discussion for future participation in the study: University Hospital Zürich, Inselspital Bern, Cantonal Hospital in Freiburg and Massachusetts General Hospital in Boston, USA. NT-proBNP was incorporated as alternative inclusion criteria to BNP.

Additional collection of 7.5ml Urine sample at admission, at 24 and 48 hours, after 6 days and before discharge was included.

The treatment schema was complemented. In the intervention group, for every medication at every time point, a tolerance margin was stablished. For standard of care group, the treatment was updated according to the latest recommendations of the European Society of Cardiology (ESC). The approach of special situations (i.e. rise in creatinine, symptomatic hypotony) was stated clearly. Eligible patients should be older than 18 years (instead of 45). To exclude the possibility of enrolling possible pregnant women, a pregnancy test is required. Inclusion of patients that were initially not in the situation to sign the ICF by him/herself, was further clarify in the protocol. Summary was updated.

Target dose of ACE-i and ARB were adjusted in the control group

Treatment schema (intervention and standard of care) for ACE-i and ARB was updated with equivalent doses for different substances within the same category. Hospital Clinic of the Faculty of Medicine University of São Paulo Brazil, University Medicine Mainz in Germany and Faculty of Medicine University of Latvia in Riga, Latvia were incorporated in the list of active centers. Biobank regulation V 1.0 was stablished in accordance with the Swiss Academy of Medical Sciences.

Acute coronary syndrome and symptomatic hypotension during initial hospitalization were listed as secondary endpoints. Exclusion criteria list was expanded to include: severe mitral stenosis, isolated right ventricular failure due to pulmonary hypertension, Systemic Lupus erythematosus and related diseases and known hypersensitivity to hydralazine or dihydralazine. Study procedures were expanded. Study scheduled was expanded. References were updated.

The Mafraq Hospital Abu Dhabi (United Arab Emirates), the Hospital Universitari Germans Trias i Pujol in Barcelona Spain, the Hospital de la Santa Creu i Sant Pau in Barcelona Spain and the University Hospital Belgrade (Serbian) were listed as participant centers. Adjustment of the cut-off from NT-proBNP and BNP for eligibility in patients with BMI > 35kg/m2 Treatment schema was updated to include Entresto (LCZ696) up titration plan in the intervention group. Measurements with the Audicor holter device would not take place anymore. Introduction of a “randomization questionnaire” as an assessment tool to measure the influence of the patient due to the open-label study design. Quality of life questionnaire will be only assess at 180 days after inclusion in the study.

Composite primary endpoint was divided and listed individually as secondary endpoints (allcause mortality at 180 days and HF rehospitalization at 180 days) University Hospital “Tsaritsa Joanna-ISUL” (Sofia, Bulgaria), the National Transport Hospital “Tsar Boris III” (Sofia, Bulgaria), the 5- th Multifunctional Hospital for Active Treatment (Sofia, Bulgaria) and the University Hospital “Alexandrovska” (Sofia, Bulgaria) were listed as participant centers. During the initial phase of treatment in the intervention groups, nitro spray (containing 0.4 mg glyceryl trinitrate per application) can be used as an alternative to nitro capsules. The change from an ACE-i and ARB to LCZ696 is possible at any time by the clinical team, both in the standard group and in the intervention group, as long as the corresponding criteria according to the current 2016 ESC Guidelines are met. SecuTrial (interActive Systems GmbH, Berlin Germany) will be used together with Microsoft Access as the study database. Centers outside Switzerland can organize their own insurance policies.