Pulmonary REsistance modification under treatment with Sacubitil/valsartaN in paTients with HeartFailure with reduced ejection fraction

Prior treatment

• Current treatment with Sacubitryl/valsartan
• Previous CRT implantation in the last 3 months or planning for CRT implantation
• A major surgery planned within 6 months of randomization
• Any situation that may make it impossible to perform the research in accordance with the protocol or express written consent in the opinion of the researcher, including abuse of alcohol, drugs or other psychoactive substances.
• Current treatment with sildenafil
• Participation in a study with a device or medicinal product within 3 months prior to randomization or 5 half-lives, whichever is longer, prior to the screening visit
• Patients ineligible or contraindicated for treatment with sacubitril/valsartan
• Documented untreated significant ventricular arrhythmia with syncope within the previous 3 months

Other illness

• Factors that prevent RHC testing (e.g. very serious condition of the patient that makes it impossible to lie down, cardiogenic shock, allergy to contrast agents, etc.)
• Acute coronary syndrome, including myocardial infarction (STEMI, NSTEMI), a condition with carotid revascularization or major cardiovascular surgery in the last 30 days
• Stroke or transient cerebral ischemia (TIA) within the last 3 months
• Severe heart Failure HF NYHA IV functional class and/or cardiogenic shock
• Severe primary valve disease (NOT secondary mitral regurgitation) or obstructive hypertrophic cardiomyopathy
• The presence of a malignant neoplasm of any organ system, ie clinical signs or no stable remission for at least 3 years after the end of the last treatment, with the exception of non-invasive basal cell carcinoma, squamous cell carcinoma of the skin or cervical epithelial dysplasia.
• Diseases that significantly reduce physical performance:- Severe COPD putting off oxygen therapy; - Severe asthma, - Morbid obesity (BMI> 40 kg / m2), - Significant lower limb atherosclerosis with intense intermittent claudication
• Uncontrolled hypertension (SBP> 170 mmHg and / or DBP> 100 mmHg)
• Patients with a history of angioedema associated with ACE I or ARB treatment
• Patients who have had a heart transplant or have had a circulatory support device
• Patient on the urgent list for heart transplant
• Isolated right heart failure secondary to lung disease

Lab values

• Severe renal failure, eGFR <30 ml / min / 1.73 m2 (calculated according to the MDRD formula)
• Serum potassium> 5.2 mEqL
• Liver failure or elevated liver transaminases (total bilirubin> 3 mg / dL and / or ALT and / or AST ≥3x ULN)

Age

• Women of childbearing age, defined as the physiological possibility of becoming pregnant, unless using two methods of contraception

Other

• Symptomatic bradycardia or second or third degree atrioventricular block not protected by a pacemaker
• Pregnant or lactating women
• Life expectancy <6 months
• Planned coronary angioplasty or pacemaker / ICD / CRT implantation within the next 6 months
• Significant lower limb atherosclerosis with intense intermittent claudication
• Symptomatic hypotension (SPB <90 mmHg)

• Age ≥18 years of age who are able to complete and sign the informed consent form.
• HF patients in NYHA II-IV in whom right heart catheterization (RHC) reveals post-capillary pulmonary hypertension (defined on the basis of the 2022 ESC guidelines as PAPm >20 mmHg and PAWP > 15 mmHg); both isolated post-capillary PH (IpcPH) (defined on the basis of the 2022 ESC guidelines as PVR <= 2 WU) as well as combined post- and pre-capillary PH (CpcPH) (defined on the basis of the 2022 ESC guidelines as PVR > 2WU).
• Stable patients haemodynamics, which is defined as no change in diuretic use for at least 4 weeks prior to study entry
• Heart failure during optimal treatment with ACE-I / ARB, beta blocker, MRA, SGLT2i except in cases where the above-mentioned treatment was contraindicated or not tolerated
• Understanding and acceptance of the research assumptions and methods and signing the informed consent by the patient