Sacubitril-valsartan in Patients With Heart Failure.

* A 3-month, prospective interventional study, which will include 60 patients with heart failure reduced ejection fraction, patients, will be consecutively randomized into two groups, the first group (n=30) will be given Sacubitril-valsartan twice daily and the second group (n=30) on standard treatment of heart failure.
* Approval will be obtained from Research and Ethics Committee of Faculty of Pharmacy, Damanhour University. Patients will provided written informed consent and will be checked for inclusion and exclusion criteria.
* All patients will undergo analysis of inflammatory biomarkers such as: NT-proBNP, Galectin-3 and GDF-15 at beginning of the study and after 3 months of the study.
* Echocardiography study before and after the study focusing on:

Measurement of parameters such as: Left atrial diameter (LAD), basic left ventricular dimensions (EDD and ESD), Ejection fraction (EF%).

\- Follow up will be performed for assessing:

1. MACE such as MI, stroke, HF, or death.
2. LV Echocardiography improvements of any of basic Echo parameters.
3. Assessment of New York Heart association (NYHA) class.

Outcomes: all patients will be followed up for 3 months for:

* 1ry outcomes: A.Major Adverse Cardiovascular Events (MACE) such as MI, stroke or death. B.Heart failure hospitalization C.LV Echocardiography improvements of any of basic Echo parameters such as: Left atrial diameter (LAD), basic left ventricular dimensions (EDD and ESD), Ejection fraction (EF%).
* 2ry outcomes: Change in inflammatory markers such as: NT-proBNP, GDF-15 and Galectin-3.

• Sacubitril-valsartan (Drug), also known as Entresto: patients (n=30) will be given Sacubitril-valsartan 50 mg twice daily.
• standard treatment of heart failure (Drug), also known as Beta blockers, ACEis: Control group (n=30) on standard treatment of heart failure.

Primary outcomes

• MACE incidence [3 months]: Major Adverse Cardiovascular Events (MACE) such as MI, stroke or death.
• Ejection fraction (EF%) [3 months]: Ejection fraction (EF%) improvement.

Secondary outcomes

• NT-proBNP level (pg/ml) [3 months]: Change in NT-proBNP level
• Galectin-3 level (pg/ml) [3 months]: Change in Galectin-3 level
• GDF-15 level (pg/ml) [3 months]: Change in GDF-15 level

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

* Age ≥ 18 years old for both genders.
* LV ejection fraction (LVEF) ≤40%.
* Heart failure patients with NYHA grade II-IV.

Exclusion Criteria:

1. CKD with GFR < 20 ml/min/1.73
2. Serum potassium < 5.5 mmol / L.
3. Pregnant or lactating women
4. Active infection.
5. Congenital heart disease.
6. Autoimmune disorders or connective tissue disorders.
7. Severe hepatic dysfunction.

• Lu H, Claggett BL, Packer M, Lam CSP, Swedberg K, Rouleau J, Zile MR, Lefkowitz M, Desai AS, Jhund P, McMurray JJV, Solomon SD, Vaduganathan M. Effects of Sacubitril/Valsartan on All-Cause Hospitalizations in Heart Failure: Post Hoc Analysis of the PARADIGM-HF and PARAGON-HF Randomized Clinical Trials. JAMA Cardiol. 2024 Nov 1;9(11):1047-1052. doi: 10.1001/jamacardio.2024.2566. PMID 39210725
• Lee YH, Lin PL, Chiou WR, Huang JL, Lin WY, Liao CT, Chung FP, Liang HW, Hsu CY, Chang HY. Combination of ivabradine and sacubitril/valsartan in patients with heart failure and reduced ejection fraction. ESC Heart Fail. 2021 Apr;8(2):1204-1215. doi: 10.1002/ehf2.13182. Epub 2021 Jan 6. PMID 33410280

• Nouran A. Abu Shaara, Bachlore, Principal investigator, Damanhour University