Adrenomedullin and Heart Failure

The plasma concentration of adrenomedullin is increased in patients with heart failure in relation to NYHA classification (40,41) (Fig. 6). Plasma adrenomedullin levels positively correlate with plasma ANP levels and with LV end-diastolic pressure (LVEDP). Blood sampling in a subset of patients with heart failure undergoing cardiac catheterization revealed a modest but significant 20% increase in adrenomedullin concentration between the aorta and the anterior interventricular vein and between the aorta and the coronary sinus, whereas the increase in ANP concentrations in the same patients was between 200 and 300%. These results show that the failing heart secretes adrenomedullin; however, adrenomedullin is also synthesized in the vasculature of the lower extremities (25). It is likely that the heart is not the only source of elevated plasma adrenomedullin in heart failure. In a study by Pousset et al. (42), the plasma concentration of adrenomedullin was a signifi

NYHA Classification

Fig. 6. Adrenomedullin (ADM) concentration in healthy control subjects and in patients with congestive heart failure according to NYHA classification. (Reproduced from ref. 40.)

Normal II

NYHA Classification

Fig. 6. Adrenomedullin (ADM) concentration in healthy control subjects and in patients with congestive heart failure according to NYHA classification. (Reproduced from ref. 40.)

cant predictor of outcome (death or cardiac transplantation) in patients with heart failure with a range ofNYHA functional classes and different etiologies. Moreover, plasma adrenomedullin was an independent predictor of outcome in multivariable models in which the only other independent predictors were ET-1 and systolic BP (BNP was not measured in this study).

In a study by Richards et al. (43), adrenomedullin and NT-proBNP were evaluated for prognostic utility in patients with LV dysfunction, and for their ability to predict benefit from treatment with the ^-blocker carvedilol in patients with chronic, stable heart failure of ischemic etiology (NYHA class II-III). Prerandomization plasma levels ofboth adreno-medullin and NT-proBNP that were above the median were more robust than ejection fraction in predicting all-cause mortality, heart failure mortality, and worsening heart failure. Both adrenomedullin and NT-proBNP were independent predictors of outcomes. More important, this study also showed that elevated adrenomedullin (as well as NT-proBNP) levels prior to treatment with carvedilol were associated with a benefit from the addition of the ^-blocker.

Infusion ofadrenomedullin in patients with heart failure and in healthy subjects decreases mean arterial pressure and increases cardiac index in both groups and decreases pulmonary capillary wedge pressure and pulmonary arterial pressure in patients with heart failure (44). Adrenomedullin also increases urine volume and urinary sodium excretion, with a decline in plasma aldosterone concentration in patients with heart failure. These results suggest that adrenomedullin, in addition to its usefulness as a biomarker, may be of potential therapeutic benefit in heart failure.

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