Background and Objectives: The aim of this paper is to evaluate the impact of humoral substance mid-regional pro-adrenomedullin (MR-proADM) on the two-year survival of patients with chronic heart failure and relate it to the dosage of furosemide. Materials and Methods: The data is taken from the stable systolic heart failure (EF < 50%) FAR NHL registry (FARmacology and NeuroHumoraL activation). The primary endpoint at two-year follow-up was death, heart transplantation, or LVAD implantation. Results: A total of 1088 patients were enrolled in the FAR NHL registry; MR-proADM levels were available for 569 of them. The mean age was 65 years, and 81% were male. The aetiology of HF was ischemic heart disease in 53% and dilated cardiomyopathy in 41% of patients. The mean EF was 31 ± 9%. Statistically significant differences (p < 0.001) were obtained in several parameters: patients with higher MR-proADM levels were older, rated higher in NYHA class, suffered more often from lower limb oedema, and had more comorbidities such as hypertension, atrial fibrillation, diabetes, and renal impairment. MR-proADM level was related to furosemide dose. Patients taking higher doses of diuretics had higher MR-proADM levels. The mean MR-proADM level without furosemide (n = 122) was 0.62 (±0.55) nmol/L, with low dose (n = 113) 1−39 mg/day was 0.67 (±0.30) nmol/L, with mid dose (n = 202) 40−79 mg/day was 0.72 (±0.34) nmol/L, with high dose (n = 58) 80−119 mg/day was 0.85 (±0.40) nmol/L, and with maximum dose (n = 74) ≥120 mg/day was 1.07 (±0.76) nmol/L, p < 0.001. Patients with higher MR-proADM levels were more likely to achieve the primary endpoint at a two-year follow-up (p < 0.001) according to multivariant analysis. Conclusions: Elevated plasma MR-proADM levels in patients with chronic heart failure are associated with an increased risk of death and hospitalization. Higher MR-proADM levels in combination with increased use of loop diuretics reflect residual congestion and are associated with a higher risk of severe disease progression.

1st Department of Internal Medicine Cardioangiology St Anne's University Hospital Faculty of Medicine Masaryk University 625 00 Brno Czech Republic

Department of Cardiology Na Homolce Hospital 150 00 Prague Czech Republic

Department of Internal Cardiology Medicine Faculty Hospital Brno Faculty of Medicine Masaryk University 625 00 Brno Czech Republic

Department of Internal Medicine Geriatrics and Practical Medicine Faculty Hospital Brno Faculty of Medicine Masaryk University 625 00 Brno Czech Republic

Department of Pathological Physiology Faculty of Medicine Masaryk University 625 00 Brno Czech Republic

Institute of Biostatistics and Analyses Faculty of Medicine Masaryk University 625 00 Brno Czech Republic

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