Mineralocorticoid receptor antagonism ameliorates left ventricular diastolic dysfunction and myocardial fibrosis in mildly symptomatic patients with idiopathic dilated cardiomyopathy - A pilot study
Mineralocorticoid receptor antagonism ameliorates left ventricular diastolic dysfunction and myocardial fibrosis in mildly symptomatic patients with idiopathic dilated cardiomyopathy - A pilot study
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DOI：
10.1161/circulationaha.105.571653
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发表时间：
2005-11-08
期刊：
影响因子：
37.8
通讯作者：
Yokota, M
中科院分区：
文献类型：
--
作者：
Izawa, H;Murohara, T;Yokota, M
背景：盐皮质激素受体拮抗剂降低心力衰竭相关死亡率的机制尚不清楚。盐皮质激素受体拮抗剂螺内酯对左心室（LV）功能和室壁僵硬度与心肌纤维化的影响进行了研究，在轻度症状的特发性扩张型心肌病（DCM）患者。方法和结果25例DCM患者纽约心脏协会功能分类I或II进行了检查之前和之后的螺内酯治疗12个月。同时测量左心室压力和容积，并获得左心室肌内膜活检标本。测定血清I型胶原羧基末端前肽（PIP）和羧基末端肽（CITP）浓度。根据血清PIP/CITP比值（心肌胶原积聚指数）将患者分为2组（35例，B组，n = 13）。基线时，B组的LV舒张室硬度、胶原体积分数以及活检组织中I型和III型胶原mRNA的丰度均大于A组，LV舒张早期应变率（组织多普勒超声心动图）小于A组。B组患者接受安体舒通治疗后，这些差异和PIP/CITP的差异显著降低，而A组治疗对这些参数无影响。胶原蛋白体积分数显着相关PIP/CITP，左心室舒张早期应变率，左心室舒张室僵硬度为所有患者的治疗前和治疗后，与spironolactone. Conclusions-螺内酯改善左心室舒张功能障碍和减少室僵硬度与轻度症状的DCM患者心肌纤维化的回归。然而，这些作用似乎仅限于心肌胶原积聚增加的患者。
Background-Mineralocorticoid receptor antagonism reduces mortality associated with heart failure by mechanisms that remain unclear. The effects of the mineralocorticoid receptor antagonist spironolactone on left ventricular (LV) function and chamber stiffness associated with myocardial fibrosis were investigated in mildly symptomatic patients with idiopathic dilated cardiomyopathy (DCM).Methods and Results-Twenty-five DCM patients with a New York Heart Association functional class of I or II were examined before and after treatment with spironolactone for 12 months. LV pressures and volumes were measured simultaneously, and LV endomyocardial biopsy specimens were obtained. Serum concentrations of the carboxyl-terminal propeptide ( PIP) and carboxyl-terminal telopeptide (CITP) of collagen type I were measured. The patients were divided into 2 groups on the basis of the serum PIP/CITP ratio ( 35, group B, n = 13), an index of myocardial collagen accumulation. LV diastolic chamber stiffness, the collagen volume fraction, and abundance of collagen type I and III mRNAs in biopsy tissue were greater and the LV early diastolic strain rate (tissue Doppler echocardiography) was smaller in group B than in group A at baseline. These differences and the difference in PIP/CITP were greatly reduced after treatment of patients in group B with spironolactone, with treatment having no effect on these parameters in group A. The collagen volume fraction was significantly correlated with PIP/CITP, LV early diastolic strain rate, and LV diastolic chamber stiffness for all patients before and after treatment with spironolactone.Conclusions-Spironolactone ameliorated LV diastolic dysfunction and reduced chamber stiffness in association with regression of myocardial fibrosis in mildly symptomatic patients with DCM. These effects appeared limited, however, to patients with increased myocardial collagen accumulation.