The Gut Microbiome in Chronic Heart Failure

The patient sample will be divided into three main groups based on clinical phenotypes determined by echocardiographic examination:

HF with preserved ejection fraction (EF) (EF > 50%) HF with mildly reduced EF (EF 49-40%) HF with reduced EF (EF < 40%) From each subgroup, 60 patients will be randomly selected to participate in a double-blind, randomized, placebo-controlled trial of probiotic therapy.

The control group will consist of individuals selected from outpatient clinics in the city of Astana, matched by gender and age, who are healthy in terms of cardiovascular and other systemic pathologies, not in an acute phase of any illness, willing to participate in the study, and have signed informed consent.

For each patient, a medical history will be collected, a physical examination will be performed to assess their clinical condition, the severity of heart failure symptoms will be evaluated using a severity scale (ANA/ACC), functional classes will be determined according to NYHA (6-minute walk test), echocardiographic examination will be conducted, and if indicated, electrocardiogram (ECG) monitoring using a Holter monitor will be performed. The physical examination will include lung auscultation, cardiac auscultation, assessment of peripheral edema, assessment of jugular venous pulse height, body weight, height, and height at the age of 20. Further investigations will be guided by symptoms. Echocardiographic examination will be performed using a diagnostic ultrasound device, Philips Ultrasound Inc., CX50. The 12-lead ECG will be recorded in the supine position. ECG intervals (PR, QRS, QT, QTc), heart rate, and any abnormalities (rhythm anomalies, AV block, pathological Q waves, bundle branch block, repolarization disturbances) will be recorded for each subject.

Clinical and laboratory parameters:

The following analyses will be performed:

• Complete blood count with differential leukocyte count
• Total/direct bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH)
• Total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides
• Serum glucose, glycosylated hemoglobin (HbA1c)
• Blood electrolytes (sodium, potassium, chloride), creatinine, blood urea nitrogen (BUN), uric acid
• Glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, gamma-glutamyl transferase (GGT)
• Creatine phosphokinase, troponin I
• Thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4)

Inclusion criteria

• Age over 18 years
• Residing in the city of Astana and surrounding regions (Akmola region)
• Diagnosis of heart failure according to internationally recognized guidelines and classified as Class I-IV by NYHA (New York Heart Association) or Stage A-C according to ACC/AHA (American College of Cardiology/American Heart Association) classification
• Clinically stable condition and optimized medication therapy for heart failure for at least 4 weeks in accordance with current recommendations
• Willingness to participate in the study

Exclusion criteria

• • Age under 18 years

• Refusal to undergo diagnostic procedures specified in the study protocol
• Terminal stage of heart failure (Stage D according to ACC/AHA classification)
• Coronary or peripheral revascularization procedures, valvular procedures, or any major surgical procedure within 3 months prior to study enrollment
• Use of antibiotics, cytostatic therapy, or pro- or prebiotics within 1 month prior to the baseline visit
• Presence of oncological and autoimmune diseases (connective tissue diseases, gastrointestinal disorders, skin disorders, etc.)
• Acute illness or active infection
• Individual intolerance to the administered nutrients (probiotics)
• Presence of other anatomical or comorbid conditions, or other medical, social, or psychological conditions that, in the investigator's opinion, may limit the subject's ability to participate in the clinical study, comply with the requirements of subsequent follow-up, or affect the scientific validity of the clinical study results.