The cyclic guanosine monophosphate/B-type natriuretic peptide ratio and mortality in advanced heart failure

Attenuation of the effects of natriuretic peptides has been demonstrated in animal models but studies in humans are scarce, particularly concerning renal attenuation. We investigated the attenuation of B-type natriuretic peptide (BNP) in chronic advanced heart failure (HF). We included 62 outpatients with HF and severe left ventricular systolic dysfunction. Cases had at least one hospital admission or emergency department visit for acute HF in the previous year and were in NYHA class III/IV despite optimized therapy. The individual age- and sex-matched controls were symptomatically controlled (NYHA I and II). We collected 24 h urine and a blood sample from all patients. Plasma BNP and plasma (pcGMP) and urine cyclic guanosine monophosphate (ucGMP) were measured. Patients were followed for 3 months for hospital admission or all-cause death. ucGMP to plasma BNP (ucGMP/BNP) ratio was attenuated in cases vs. controls [median (IQR): 8354 (4293-16 456) vs. 12 693 (6896-22 851)]. There were no differences in pcGMP to BNP (pcGMP/BNP) ratio or urine cGMP excretion. Patients with worse outcome had lower pcGMP/BNP [260 (86-344) vs. 381 (244-728) in patients without adverse outcome events] and lower ucGMP/BNP [4146 (2207-9363) vs. 10 922 (7495-19 971)]. Renal NP's second messenger production is attenuated in advanced HF. Patients with worse outcome have lower ucGMP/BNP and pcGMP/BNP ratios.