Activity of GH/IGF-I axis in patients with dilated cardiomyopathy

OBJECTIVE There is evidence showing that GH and IGF-I have specific recepto rs in the heart and that these hormones are able to promote cardiac remodel ling and inotropism. It has been reported that patients with dilated cardio myopathy (DCM) benefit from treatment with rhGH showing a striking increase in cardiac contractility. However, until now, the activity of GH/IGF-I axi s in DCM has never been clearly assessed. PATIENTS To clarify this point, we enrolled 39 patients with idiopathic or post-ischaemic DCM (36 M/3 F; age (mean +/- S.D.) 55.3 +/- 9.0 years; BMI: 25.3 +/- 3.2 kg/m(2); New York Heart Association class (NYHA) I/2, II/19, I II/15, IV/3) and 42 age-matched controls (CS, 38 M/4 F; age 56.0 +/- 7.8 ye ars; BMI: 24.9 +/- 1.5 kg/m(2)). DCM patients were characterized by a left- ventricular diastolic diameter of 73.8 +/- 8.3 mm, a shortening fraction of 15.9 +/- 6.4% and a left ventricular ejection fraction of 25.1 +/- 8.7%. I n all subjects clinical and biochemical indices of renal and hepatic functi on as well as nutritional parameters were in the normal range. MEASUREMENTS In both groups we studied: a) IGF-I levels in basal conditions and after administration of low rhGH doses for 4 days (5.0 or 10.0 mu/kg/d ay x 4 days); b) the acute OH-response to GHRH (1.0 mu/kg i.v.) or hexareli n (HEX, 2.0 mu/kg i.v.), a peptidyl GH secretagogue (GHRP); c) mean GH conc entration (mGHc) over 10 h sampling (every 20 min) from 2200 h to 0800 h. RESULTS Basal IGF-I levels in DCM were lower (P=0.000039) than in CS (135.2 +/- 46.8 vs. 193.7 +/- 63.7 mu/l), whereas, basal IGFBP-3 and GHBP2 levels in DCM and CS were similar (2.5 +/- 1.3 vs. 2.6 +/- 0.5 mg/l and 25.3 +/- 3.6 vs. 28.3 +/- 5.0%; P=0.95 and P=0.085, respectively). After 4 days of 5 .0 mu/kg/day rhGH administration, IGF-I levels in DCM (215.4 +/- 82.0 mu/l; P=0.0023 vs. baseline) remained lower (P=0.027) than those in CS (280.0 +/ - 80.7 mu/l; P=0.000080 vs. baseline). After 10.0 mu/kg/day for 4 days, IGF -I levels in DCM (297.2 +/- 109.2 mu/l; P=0.0033 vs, baseline) were similar (P=0.76) to those in CS (310.9 +/- 81.7 mu/l; P=0.000060 vs, baseline). Th e GH response to GHRH in DCM was lower (P=0.0022) than that in CS (hAUC(0-- >120): 192.0 +/- 177.3 vs. 345.3 +/- 191.1 mu/l/h) whereas that to HEX in D CM and CS was similar (611.0 +/- 437.5 vs. 535.4 +/- 302.8 mu/l/h; P=0.95). Within the DCM group, basal and rhGH-stimulated IGF-levels as wel as the G H response to GHRH or HEX were not different among NYHA classes and did not show any correlation with ECHO parameters. The mGHc in DCM (1.0 +/- 0.5 mu /l) was similar (P=0.57) to that in CS (0.9=0.7 mu/l). CONCLUSIONS Our present data demonstrate that in dilated cardiomyopathy pat ients with severe left ventricular dysfunction basal IGF-I levels are reduc ed whereas the IGF-I response to low rhGH doses is preserved. These finding s suggest a normal peripheral GH sensitivity in dilated cardiomyopathy. On the other hand, though nocturnal mean GH concentration in dilated cardiomyo pathy patients is similar to that in normal subjects, the somatotroph respo nsiveness to GHRH, but not that to hexarelin, is reduced. Thus, subtle alte rations in the activity of GH/IGF-I axis are present in dilated cardiomyopa thy.