Even in stable low-risk outpatients with NICM at 6 months after hospital discharge for decompensated HF, BNP assessment predicts a long-term risk of redecompensation.

SUMMARYCyclic GMP (cGMP) serves as an intracellular second messenger of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and nitric oxide (NO) and its peripheral blood concentration is an index of its biological activity. It has been reported that the plasma concentration of cGMP is correlated with the concentrations of ANP and BNP and is related to the prognosis of chronic heart failure patients, but the relation with NO has not been studied. Therefore, we investigated the roles of ANP, BNP, and NO in relation to cGMP in the blood during worsening and improvement of chronic heart failure. The subjects were 25 patients who were hospitalized in our hospital for acute worsening of chronic heart failure. Plasma concentrations of NO, norepinephrine (NE), ANP, BNP, and cGMP were measured on acute worsening (admission) and improvement (discharge) of heart failure. The cGMP concentration on worsening showed a positive correlation with the NO concentration (r = 0.57, P < 0.01), but no correlations with ANP or BNP were observed. The cGMP concentration on improvement showed no correlation with the NO concentration, but a positive correlation with ANP (r = 0.69, P < 0.001) and BNP (r = 0.67, P < 0.001). No correlation was observed between the NO and NE concentrations. We also studied serious cases of NYHA IV and mild cases of NYHA II to III. The cGMP concentration in the serious group showed a positive correlation with the NO concentration but no correlations with ANP or BNP concentrations on worsening. However, in the mild group, the cGMP concentration during worsening showed positive correlations with both the NO and BNP concentrations. On improvement, the cGMP concentration showed no correlation with the NO concentration but positive correlations with both the ANP and BNP concentrations in both the severe and mild groups. The results suggest the possibility that cGMP is produced mainly by NO during worsening, and by ANP and BNP rather than NO during improvement of chronic heart failure. (Jpn Heart J 2003; 44: 713-724)

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A highly sensitive radioimmunoassay to measure atrial natriuretic peptide (ANP) concentration in urine has been established, and its clinical usefulness is presented. ANP in urine was stable at 4 degrees C for several days and was easily measured by our radioimmunoassay. The average ANP excretion in 65 healthy persons was 25.0 +/- 1.4 ng/day (mean +/- SEM) and the fractional excretion of ANP was 0.7 +/- 0.05%. In 14 patients with congestive heart failure, the average ANP excretion was 119.2 +/- 29.4 ng/day, which decreased to 53.3 +/- 11.0 after successful treatment.

In the present study, an attempt was made to clarify whether ANP molecular forms in the plasma of severe congestive heart failure patients differ from those in healthy persons and whether ANP molecular forms in the plasma of the patients were changed by successful treatment of cardiac disease. Twenty patients with congestive heart failure were treated at Kitasato University Hospital. They were classified as class III or IV by New York Heart Association criteria at the time of admission. Plasma ANP concentrations decreased after treatment from 356 +/- 58.2 to 72.3 +/- 14.8 pg/ml. The gel permeation chromatograms from the plasma of healthy persons showed low, or low and high molecular weight ANP peaks which correspond to the elution positions of authentic alpha-ANP or ribonuclease A (mol. wt., 13.7 kdalton). In patients with severe congestive heart failure at a severe stage, middle molecular weight ANP consisted with the elution position of authentic beta-ANP was particularly noted in addition of low and high molecular weight ANP peaks. This middle molecular weight peak disappears in most of cases by successful treatment. Molecular forms in the plasma obtained from the coronary sinus and the inferior or superior vena cava were essentially the same. These results indicate that the middle molecular weight ANP supposed as beta-ANP may particularly be secreted in severe congestive heart failure patients.