TY - JOUR
T1 - Chronic inhibition of cGMP phosphodiesterase 5A improves diabetic cardiomyopathy
T2 - A randomized, controlled clinical trial using magnetic resonance imaging with myocardial tagging
AU - Giannetta, Elisa
AU - Isidori, Andrea M.
AU - Galea, Nicola
AU - Carbone, Iacopo
AU - Mandosi, Elisabetta
AU - Vizza, Carmine D.
AU - Naro, Fabio
AU - Morano, Susanna
AU - Fedele, Francesco
AU - Lenzi, Andrea
PY - 2012/5/15
Y1 - 2012/5/15
N2 - Background-cGMP phosphodiesterase type 5 protein is upregulated in myocardial hypertrophy. However, it has never been ascertained whether phosphodiesterase type 5 inhibition exerts an antiremodeling effect in nonischemic heart disease in humans. We explored the cardioreparative properties of a selective phosphodiesterase type 5 inhibitor, sildenafil, in a model of diabetic cardiomyopathy. Methods and Results-Fifty-nine diabetic men (60.3±7.4 years) with cardiac magnetic resonance imaging consistent with nonischemic, nonfailing diabetic cardiomyopathy (reduced circumferential strain [σ],-12.6±3.1; increased left ventricular [LV] torsion [θ], 18.4±4.6°; and increased ratio of LV mass to volume, 2.1±0.5 g/mL) were randomized to receive sildenafil or placebo (100 mg/d). At baseline, the metabolic indices were correlated with torsion, strain, N-terminal pro-B-type natriuretic peptide, vascular endothelial growth factor, monocyte chemotactic protein-1, and blood pressure. After 3 months, sildenafil produced a significant improvement compared with placebo in LV torsion (Δθ: sildenafil,-3.89±3.11° versus placebo, 2.13±2.35°; P
AB - Background-cGMP phosphodiesterase type 5 protein is upregulated in myocardial hypertrophy. However, it has never been ascertained whether phosphodiesterase type 5 inhibition exerts an antiremodeling effect in nonischemic heart disease in humans. We explored the cardioreparative properties of a selective phosphodiesterase type 5 inhibitor, sildenafil, in a model of diabetic cardiomyopathy. Methods and Results-Fifty-nine diabetic men (60.3±7.4 years) with cardiac magnetic resonance imaging consistent with nonischemic, nonfailing diabetic cardiomyopathy (reduced circumferential strain [σ],-12.6±3.1; increased left ventricular [LV] torsion [θ], 18.4±4.6°; and increased ratio of LV mass to volume, 2.1±0.5 g/mL) were randomized to receive sildenafil or placebo (100 mg/d). At baseline, the metabolic indices were correlated with torsion, strain, N-terminal pro-B-type natriuretic peptide, vascular endothelial growth factor, monocyte chemotactic protein-1, and blood pressure. After 3 months, sildenafil produced a significant improvement compared with placebo in LV torsion (Δθ: sildenafil,-3.89±3.11° versus placebo, 2.13±2.35°; P
KW - cardiac magnetic resonance imaging
KW - diabetes mellitus type 2
KW - diabetic diastolic heart failure
KW - fibrosis
KW - phosphodiesterase inhibitors heart failure
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U2 - 10.1161/CIRCULATIONAHA.111.063412
DO - 10.1161/CIRCULATIONAHA.111.063412
M3 - Article
C2 - 22496161
AN - SCOPUS:84861234413
VL - 125
SP - 2323
EP - 2333
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 19
ER -