Metabolic Response to Iniciation of Heart Failure Therapy
This protocol is part of the CarDia project - National Institute for Metabolic and Cardiovascular Disease Research (EXCELES Program, ID: LX22NPO5104), funded by the European Union - Next Generation EU. The protocol is part of Work Package 5 (WP5): metabolic disorders in heart failure.

The goal of this observational protocol is to monitor the biochemical and metabolomic response to the initiation of therapy for heart failure with standard drugs (SGLT2i, sGC stimulators, ARNI) and whether this early response (within first 3 months) predicts the further course of the disease.

The protocol will examine how parameters reflecting neurohumoral activation, response to hypoxia, systemic metabolism of energy substrates, parameters of iron metabolism, HIF1A activation in peripheral blood behave over time after starting standard heart failure terapiy (baseline, 1 day, 1 week, 1 month, 3 month). This project can provide valuable information on how to identify people who respond more poorly to the treatment being introduced and are more at risk of an adverse course of the disease. Patients will be compared to patients who have no change of therapy over early observation period (3 mo), who will serve as controls. This is observational study, so decision to inicialize therapy will be based on medical indication.

Patients with heart failure treated at the IKEM Cardiocenter will have blood drawn at several defined intervals before and after the start of clinically indicated treatment. Some patients will also undergo genetic DNA testing to determine the variability of genes regulating the metabolic neurohumoral response to heart failure. Patients will be contacted at intervals of 1 and 2 years and the incidence of clinical events will be monitored. The study is observational in nature and inclusion in the study does not affect the course of care provided or the choice of pharmacotherapy.
- EligibilityCriteria: Inclusion Criteria:  ability to give written informed consent Heart failure NYHA II-IV with duration &gt; 3 months (regardless EF, universal definition of HF) NTproBNP: &gt; 125 pg/ml at screening (Bozkut Univ. definition of HF) O2 sat &gt; 90%  Exclusion Criteria:  Previous gliflozin or i.v., iron therapy in past 3 months (for SGLT2i arm) Previous sGC stimulator (for sGC arm) Previous ARNI (for ARNI arm) Previous SGLT2i, sGC or ARNI for control group. CABG, CRT, STEMI, valve replacement, in past 3 months, or planned within next 3 months Blood loss needing transfusion in past 3 months Clinical instability (including HF hospitalization) in the past 1 month Myelodysplasia, chronic hemolysis, EPO therapy Systemic inflammatory condition (lupus, rheumatoid arthritis...), infection Uncontrolled cancer CKD grade 4-5 Severe anemia with Hgb &lt; 90 g/L No chronic exposure to hypoxia (severe COPD, OSA, long-term oxygen therapy) History of SGLT2i allergy or intolerance Repeated genitourinary infection - HealthyVolunteers: No - Gender: All - MinimumAge: 18 Years - StdAgeList: Adult, Older Adult - StudyPopulation: Stable HF patients with HFrEF, HFmrEF or HFpEF - SamplingMethod: Non-Probability Sample