The aim of this study is to determine whether and how serum concentrations of the used medicinal products, including their metabolites, correlate with selected clinical indicators of heart failure (NT-proBNP concentration, 6-minute walk test, quality of life questionnaire, echocardiographic parameters, hospitalization for HFrEF, length of survival).

The prevalence of chronic heart failure increases with age, and this disease is one of the most common reasons for hospitalization in the elderly. In order to reduce the number of exacerbations, the frequency of hospitalizations, morbidity and mortality and improve the overall quality of life, the treatment strategy should be individually set for each patient, regularly monitored and reviewed.

Patients with chronic heart failure show significant differences in the pharmacokinetics of both cardiovascular and non-cardiovascular drugs. At the same time, they tend to be exposed to other prescribed medicinal products, and therefore there is an increased risk of drugs interactions. These findings emphasize the need for comprehensive pharmacokinetic studies in patients with chronic heart failure, together with the exploration of the potential benefit of biomarkers suitable for monitoring the clinical status of patients. Pharmacotherapy of chronic heart failure with reduced ejection fraction (Heart Failure with Reduced Ejection Fraction - HFrEF) currently consists of beta-blockers together with mineralocorticoid receptor antagonists, the combination of sacubitril/valsartan drugs and sodium-glucose transporter 2 inhibitors. Although the recommendation of therapeutic drug monitoring (TDM) in patients with chronic heart failure has not yet been established, its introduction can serve as an effective tool for detecting changes in the pharmacokinetics of drugs used, objectifying drug interactions and ascertaining patient adherence to treatment, thereby becoming part of safe personalized pharmacotherapy of this disease.

Inclusion Criteria:

• HFrEF with already established or newly started treatment with the listed medicinal products
• Male and female patients over 18 years of age
• Signed Informed Consent with participation in the study
• Women of childbearing potential must have a negative serum human chorionic gonadotropin (hCG) result at baseline and use an acceptable method of contraception with a home control urine pregnancy test every 3 months throughout the duration of the study

Exclusion Criteria:

• Hypersensitivity to the medicinal substance or to any auxiliary substance
• Pregnant and breastfeeding women
• Additional exclusion criteria for patients taking Bisoprolol, Carvedilol, Metoprolol succinate or Nebivolol: Unstable or decompensated heart failure belonging to New York Heart Association (NYHA) group IV according to the New York Heart Association classification, requiring intravenous inotropic support
• Additional exclusion criteria for patients using Bisoprolol, Carvedilol, Metoprolol succinate or Nebivolol:
• - Clinically manifest liver dysfunction
• - History of bronchospasm or asthma
• - Severe obstructive airways disease
• - 2nd and 3rd degree A-V block (unless a permanent pacemaker is implanted)
• - severe bradycardia (heart rate <50)
• - 2nd and 3rd degree A-V block (unless a permanent pacemaker is implanted)
• - severe bradycardia (heart rate <50)
• - cardiogenic shock
• - sinus node dysfunction syndrome (including sinoatrial block)
• - severe hypotension (systolic blood pressure <85 mmHg)
• - Prinzmetal angina
• - untreated pheochromocytoma
• - metabolic acidosis
• - severe peripheral arterial circulation disorders
• - concurrent intravenous treatment with verapamil or diltiazem
• Additional exclusion criteria for patients using Spironolactone:
• - anuria
• - acute renal failure
• - severe renal impairment (estimated glomerular filtration rate <10 ml/min)
• - hyperkalemia >5.5 mmol/l
• - hyponatremia <125 mmol/l
• - Addison's disease
• - concurrent use of eplerenone or other potassium-sparing diuretics
• - porphyria
• Additional exclusion criteria for patients using Sacubitril/Valsartan:
• - concomitant use with Angiotensin converting enzyme (ACE) inhibitors
• - angioedema related to previous ACE inhibitor treatment or a history of angiotensin II receptor blockers (ARB) treatment
• - hereditary or idiopathic angioedema
• - concomitant use with medicinal products containing Aliskiren in patients with diabetes mellitus or in patients with impaired renal function (eGFR <60 ml/min/1.73 m2)
• - severe liver dysfunction, biliary cirrhosis and cholestasis

There is no plan to share individual participant data with other researchers.