The purpose of this study is to determine if cachexia and changes in body composition influence pharmacokinetics of bisoprolol and ramipril and the accuracy of equations for renal function estimation.

Patients with chronic heart failure on treatment with bisoprolol and/or ramipril will be included. Study will consist of two study visits: baseline visit (V1) and visit which will be performed at least 6 months after baseline (V2). At both visits same procedures will be performed. On the day of the visit, patients will be asked to take their morning dose of bisoprolol and/or ramipril after the withdrawal of the first morning plasma sample. Additional 3 to 5 plasma samples will be taken within 5 hours post bisoprolol and/or ramipril dose in order to determine pharmacokinetic profile of both drugs. Body composition will be measured by bioimpedance and dual-energy X-ray absorptiometry. Renal function will be measured by clearance of intravenously administered iohexol. Biochemical parameters, muscle strength, fatigue and anorexia will be assessed in order to determine presence of cachexia.

Changes in body composition will be correlated with changes in pharmacokinetic parameters of bisoprolol and ramipril. Pharmacokinetic parameters in cachectic patients will be compared to pharmacokinetic parameters in non-cachectic patients. Parameters of body composition will be correlated with the difference between measured and estimated renal function.

Inclusion Criteria:

• Diagnosis of chronic heart failure of New York Heart Association Functional Classification (NYHA) class II and III
• On treatment with bisoprolol for at least 3 days and/or ramipril for at least 4 days before V1
• Able and willing to provide freely given written informed consent

Exclusion Criteria:

• Chronic renal disease with estimated glomerular filtration rate calculated by Modification of Diet in Renal Disease (MDRD) equation < 40 mL/(min x 1,73 m2) at V1 or V2
• Liver disease or increased serum liver enzymes (bilirubin > 1.5 x normal, gamma-glutamyl transpeptidase (GGT) > 2.5 x normal, aspartate transaminase (AST) > 2.5 x normal, alanine transaminase (ALT) > 2.5 x normal) at V1 or V2
• Absence of bisoprolol or ramipril steady state concentrations at V1 or V2 or withdrawal of bisoprolol and/or ramipril in-between both visits
• Acute decompensation of heart failure in less than 4 weeks before V1 or V2
• Addition, withdrawal or change in dose of drugs that importantly influence bisoprolol or ramipril pharmacokinetics in-between V1 and V2
• Unable to understand and comply with protocol or to give informed consent

Patients with chronic heart failure who attend internal medicine outpatient clinic