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Sildenafil Improves Diabetic Cardiomyopathy

Known as a treatment for erectile dysfunction, the phosphodiesterase 5A inhibitor also improves diabetic cardiomyopathy….

Dr. Andrea M. Isidori from Sapienza University of Rome stated that, “We believe that diabetic patients with early signs of cardiac impairment are the best candidates for this treatment.” 

For their study of the systemic and cardiac effects of sildenafil, Dr. Isidori and colleagues enrolled 59 patients with nonischemic diabetic cardiomyopathy but without clinical heart failure and treated them with 100 mg/day for 3 months. Fifty-four patients completed the trial.

The primary efficacy outcome was left ventricular torsion angle, a measure of systolic function that strongly correlates with cardiac mass and geometric remodeling, the authors reported online April 11 in Circulation.

At baseline, all patients showed cardiac MRI features compatible with cardiac remodeling, including increased torsion angle, reduced circumferential strain, increased left ventricular mass index, low-normal end-diastolic volume, and increased left ventricular mass-to-volume ratio with normal output.

Compared with placebo, sildenafil produced significant improvements in torsion and strain, end-diastolic volume index, concentricity index, and cardiac performance. Sildenafil treatment was also associated with improvements in baseline midwall torsion and intramyocardial strain.

Baseline correlations between cardiac kinetic parameters, metabolic indices, and blood pressure disappeared after treatment with sildenafil (but persisted with placebo treatment), suggesting that sildenafil affects cardiac left ventricular function independently of other known determinants.

The only changes in serum inflammatory biomarkers were significant reductions in monocyte chemotactic protein (MCP)-1 and transforming growth factor (TGF)-beta in the sildenafil group, compared with placebo.

According to Dr. Isidori, the “cGMP pathway, the target of our pharmacological intervention, appears to be a modulator of cardiac response to a large number of cardiac insults or damaging conditions.” “We don’t have, as yet, sufficient evidence (trials) performed in patients with severe cardiac impairment to recommend unconditional use of PDE5 inhibitors.” “Although I am convinced that these drugs are safe, even in advanced disease, it might also be that inhibiting remodeling at late stages might be less beneficial or even harmful.”

Dr. Isidori noted, “We documented that diabetes is the trigger for development of asymptomatic cardiac hypertrophy.” “We showed that this hypertrophy, at the beginning, is of the concentric type (the one associated with thickening of the ventricular wall and decrease of the internal ventricular volume); we also showed that such ventricular remodeling is directly correlated with the severity of metabolic impairment.”

“However,” he added, “little is known on how long does it takes to produce cardiac dilation, or how far augmentation of cardiac torsion proceeds (that we measure using MR). These data are necessary to establish a treatment flow-chart and to determine how early intervention is needed to prevent the development of heart failure.”

Dr. Isidori added, “We have an ongoing follow-up study on the same cohort of patients, designed as an observational study.” “PDE5 inhibitors might become soon become the new ‘sartans,’ used early to prevent cardiac remodeling.”

CIRCULATION.111.063412, 2012, doi: 10.1161/​CIRCULATIONAHA.111.063412