47999
document
PDE5 inhibition with sildenafil improves left ventricular diastolic function , cardiac geometry , and clinical status in patients with stable systolic heart failure : results of a 1-year , prospective , randomized , placebo-controlled study . BACKGROUND In heart failure ( HF ) , a defective nitric oxide signaling is involved in left ventricular ( LV ) diastolic abnormalities and remodeling . PDE5 inhibition , by blocking degradation of nitric oxide second-messenger cyclic guanosine monophosphate , might be beneficial . In a cohort of systolic HF patients , we tested the effects of PDE5 inhibition ( sildenafil ) on LV ejection fraction , diastolic function , cardiac geometry , and clinical status . METHODS AND RESULTS Forty-five HF patients ( New York Heart Association class II-III ) were randomly assigned to placebo or sildenafil ( 50 mg three times per day ) for 1 year , with assessment ( 6 months and 1 year ) of LV ejection fraction , diastolic function , geometry , cardiopulmonary exercise performance , and quality of life . In the sildenafil group only , at 6 months and 1 year , LV ejection fraction , early diastolic tissue Doppler velocities ( E ' ) at the mitral lateral ( from 4.62 to 5.20 and 5.19 m/s ) and septal ( from 4.71 to 5.23 and 5.24 m/s ) annuli significantly increased , whereas the ratio of early transmitral ( E ) to E ' lateral decreased ( from 13.1 to 9.8 to 9.4 ) ( P < 0.01 ) . Changes were accompanied by a reverse remodeling of left atrial volume index ( from 32.0 to 29.0 and 29.1 mL/m ( 2 ) ; P < 0.01 ) and LV mass index ( from 148.0 to 130.0 and 128.0 g/m ( 2 ) ; P < 0.01 ) . Furthermore , sildenafil improved exercise performance ( peak Vo ( 2 ) ) , ventilation efficiency ( ventilation to CO ( 2 ) production slope ) , and quality of life ( P < 0.01 ) . Minor adverse effects were noted : flushing in 4 and headache in 2 treated patients . CONCLUSIONS Findings confirm that in HF , sildenafil improves functional capacity and clinical status and provide the first human evidence that LV diastolic function and cardiac geometry are additional targets of benefits related to chronic PDE5 inhibition .
48000
Intervention_Pharmacological
sildenafil
48001
Intervention_Control
placebo-controlled
48002
Intervention_Pharmacological
sildenafil
48003
Intervention_Control
placebo
48004
Intervention_Pharmacological
sildenafil
48005
Intervention_Pharmacological
sildenafil
48006
Intervention_Pharmacological
sildenafil
48007
Outcome_Physical
LV ejection fraction , diastolic function , geometry , cardiopulmonary exercise performance , and quality of life .
48008
Outcome_Physical
LV ejection fraction , early diastolic tissue Doppler velocities ( E ' ) at the mitral lateral
48009
Outcome_Physical
septal
48010
Outcome_Physical
annuli significantly
48011
Outcome_Physical
reverse remodeling of left atrial volume index
48012
Outcome_Physical
LV mass index
48013
Outcome_Physical
exercise performance ( peak Vo ( 2 ) ) , ventilation efficiency ( ventilation to CO ( 2 ) production slope ) , and quality of life
48014
Outcome_Physical
flushing
48015
Outcome_Physical
headache
48016
Outcome_Other
functional capacity and clinical status
48017
Outcome_Physical
LV diastolic function
48018
Outcome_Physical
cardiac geometry
48019
Participant_Condition
stable systolic heart failure :
48020
Participant_Condition
systolic HF
48021
Participant_Sample-size
Forty-five
48022
Participant_Condition
HF