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
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
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DOI：
10.1161/circheartfailure.110.944694
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发表时间：
2011-01-01
影响因子：
9.7
通讯作者：
Guazzi, Maurizio D.
中科院分区：
文献类型：
--
作者：
Guazzi, Marco;Vicenzi, Marco;Guazzi, Maurizio D.
背景-在心力衰竭(HF)中，一氧化氮信号的缺陷与左心室(LV)的舒张期异常和重构有关。通过阻断一氧化氮第二信使环鸟苷一磷酸的降解，抑制PDE5可能是有益的。在一组收缩期心衰患者中，我们测试了PDE5抑制剂(西地那非)对左心室射血分数、舒张期功能、心脏几何构型和临床状态的影响。方法和结果-45例心衰患者(纽约心脏协会II-III级)随机分为安慰剂或西地那非(50 mg/d，3次/d)，为期1年，评估(6个月和1年)左心室射血分数、舒张期功能、几何形状、心肺运动能力和生活质量。单用西地那非治疗6个月和1年后，二尖瓣环左室射血分数、二尖瓣环舒张早期组织多普勒血流速度(E‘)分别由4.62~5.20和5.19m/S、5.24m/S显著增加(P<0.01)，二尖瓣环与二尖瓣环E/E比值由13.1/9.8下降到9.4(P<；0.01)。左心房容量指数(32.0~29.0和29.1mL/m(2))和左心室质量指数(148.0~130.0和128.0 g/m(2)；P<；0.01)均发生逆转。此外，西地那非改善了运动能力(VO2峰值)、通风效率(通风到二氧化碳产生斜率)和生活质量(P<；0.01)。有4名患者出现轻微不良反应，2名接受治疗的患者出现头痛。结论--研究结果证实，西地那非改善了心衰患者的功能能力和临床状态，并首次为人类提供证据，证明左室舒张功能和心脏几何构型是与慢性PDE5抑制相关的额外受益目标。
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 VO2), ventilation efficiency (ventilation to CO2 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.