Increase in plasma adrenomedullin in patients with heart failure characterised by diastolic dysfunction

Abstract

Objective: To investigate the relation between plasma adrenomedullin and the severity of diastolic dysfunction in patients with heart failure.

Design: Prospective study.

Setting: University teaching hospital.

Patients: 77 patients (mean (SEM) age 66.3 (1.2) years; 75% male) who were being followed in the outpatient clinic after admission to hospital for acute heart failure.

Interventions: Same day echocardiography with Doppler studies; determination of venous adrenomedullin concentration by radioimmunoassay.

Main outcome measures: Plasma adrenomedullin concentration and its correlation with systolic and diastolic function.

Results: 31 patients (40%) had isolated diastolic dysfunction (ejection fraction > 50%), and the remaining 46 had a depressed ejection fraction (< 50%). Of the patients with diastolic dysfunction, 17 had a restrictive filling pattern. In all but one of these there was coexisting systolic failure (chi(2) = 10.7, p = 0.001). Patients with systolic heart failure and a restrictive filling pattern (group 1, n = 16) had a higher plasma adrenomedullin than those with systolic failure and a non-restrictive filling pattern (group 2, n = 30) or with isolated diastolic heart failure and a non-restrictive filling pattern (group 3, n = 30) (mean (SEM): 91.7 (21.1) v 38.4 (8.8) v 34.0 (6.5) pmol/l, both p < 0.05). All heart failure values were higher (p < 0.01) than the control value (6.9 (1.2) pmol/l). Ejection fraction and left ventricular dimensions were similar in groups 1 and 2. Plasma adrenomedullin did not correlate with ejection fraction or New York Heart Association functional class. Stepwise multiple regression analysis showed that the presence of a restrictive filling pattern was the only independent variable associated with a high plasma adrenomedullin.

Conclusions: Plasma adrenomedullin concentrations in patients with heart failure are determined by the presence of diastolic dysfunction, and are especially raised in the presence of a restrictive filling pattern. There appears to be no correlation with systolic dysfunction.

Figure 1

Mean plasma adrenomedullin concentrations in controls (white bar), all heart failure patients (HF) (hatched bar), patients with isolated diastolic heart failure (grey bar), and patients with systolic heart failure (black bar). Error bars = SEM. *p< 0.01 v controls.

Figure 2

Effect of diastolic dysfunction with restrictive filling pattern (RFP) on plasma adrenomedullin concentrations in patients with systolic heart failure (HF). (A) Patients with RFP (hatched bar) had significantly higher plasma adrenomedullin that those with a non-restrictive pattern (non-RFP) (white bar). *p < 0.05, RFP v non-RFP groups. (B) There was no difference in the left ventricular ejection fraction between RFP and non-RFP groups.