Mizuta Yoshihiko, Kai Hisashi, Mizoguchi Minori, Osada Katsunori, Tahara Nobuhiro, Nakaura Hiroyuki, Kuwahara Fumitaka, Imaizumi Tsutomu
Department of Internal Medicine, Division of Cardio-vascular Medicine and Cardiovascular Research Institute, Kurume University School of Medicine, Kurume, Japan.
Hypertens Res. 2008 Oct;31(10):1835-42. doi: 10.1291/hypres.31.1835.
Myocardial fibrosis is the major determinant of diastolic property of the left ventricle (LV). Experimental and clinical studies have suggested that angiotensin receptor blockers attenuate myocardial fibrosis in various heart diseases. The integrated backscatter signal (IBS) represents a promising ultrasonic method for assessing the characterization of myocardial tissue: cardiac cycle-dependent variation of the IBS (IBS-CV) is negatively correlated with myocardial collagen deposition in hypertensive hearts. Using non-invasive echocardiographic techniques, we performed a prospective, multi-center trial to examine whether long-term treatment with valsartan would improve myocardial fibrosis and diastolic dysfunction in hypertensives. This study included 43 hypertensive patients who had impaired diastolic function (transmitral Doppler flow early to late filling velocity ratio [E/A ratio] <1.0) and preserved systolic function (LV ejection fraction [LVEF] >50%). Twelve-month valsartan treatment reduced blood pressure (BP) and LV mass index. Valsartan significantly increased not only IBS-CV but also E/A ratio without changing LVEF. The effects of valsartan were compared between two subgroups: one with low IBS-CV (IBS-CV <5.08 dB [the average of 43 patients at baseline]), the other with high IBS-CV (IBS-CV >5.08 dB). At baseline, BP, LV mass index, LVEF, and E/A ratio were similar in the two groups. Valsartan significantly increased IBS-CV and E/A ratio in the low IBS-CV group, but not in the high IBS-CV group, despite comparable reductions in BP and LV mass. In conclusion, long-term valsartan treatment attenuated myocardial fibrosis and improved diastolic dysfunction in hypertensives. It is suggested that in the low IBS-CV group, improvement of diastolic dysfunction by valsartan may be caused by attenuation of myocardial fibrosis, and not by regression of LV hypertrophy.
心肌纤维化是左心室（LV）舒张特性的主要决定因素。实验和临床研究表明，血管紧张素受体阻滞剂可减轻各种心脏病中的心肌纤维化。背向散射积分信号（IBS）是一种很有前景的评估心肌组织特征的超声方法：IBS的心动周期依赖性变化（IBS-CV）与高血压心脏中的心肌胶原沉积呈负相关。我们使用非侵入性超声心动图技术进行了一项前瞻性、多中心试验，以研究缬沙坦长期治疗是否能改善高血压患者的心肌纤维化和舒张功能障碍。本研究纳入了43例舒张功能受损（二尖瓣血流频谱E/A比值<1.0）且收缩功能正常（左心室射血分数[LVEF]>50%）的高血压患者。缬沙坦治疗12个月可降低血压（BP）和左心室质量指数。缬沙坦不仅显著增加了IBS-CV，还显著增加了E/A比值，而LVEF未改变。将缬沙坦的疗效在两个亚组之间进行了比较：一个亚组的IBS-CV较低（IBS-CV<5.08 dB[43例患者基线时的平均值]），另一个亚组的IBS-CV较高（IBS-CV>5.08 dB）。基线时，两组的血压、左心室质量指数、LVEF和E/A比值相似。尽管血压和左心室质量的降低程度相当，但缬沙坦在低IBS-CV组中显著增加了IBS-CV和E/A比值，而在高IBS-CV组中则没有。总之，缬沙坦长期治疗可减轻高血压患者的心肌纤维化并改善舒张功能障碍。提示在低IBS-CV组中，缬沙坦改善舒张功能障碍可能是由于心肌纤维化的减轻，而非左心室肥厚的消退。
