Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
J Cardiol. 2012 Nov;60(5):416-21. doi: 10.1016/j.jjcc.2012.06.009. Epub 2012 Aug 4.
Although myocardial interstitial fibrosis has been considered to play a pathogenic role in chronic heart failure (HF), the role of perivascular fibrosis, another form of fibrosis, remains to be elucidated.
We examined 64 consecutive patients with non-ischemic HF caused by hypertrophic cardiomyopathy (HCM, n=16), hypertensive heart disease (HHD, n=11), or dilated cardiomyopathy (DCM, n=37), diagnosed by both cardiac catheterization and endomyocardial biopsy (right ventricular side of the interventricular septum) in the Tohoku University Hospital between January 2001 and April 2009. We calculated the collagen volume fraction (CVF) and perivascular fibrosis ratio (PFR) in biopsy samples and also examined Thrombolysis in Myocardial Infarction (TIMI) frame count to evaluate coronary blood flow.
There was no significant correlation between CVF and PFR (r(2)=0.0007). Although CVF was comparable among HCM, HHD, and DCM (1.11 ± 1.04, 1.89 ± 1.61, and 1.41 ± 1.48, respectively), PFR was significantly higher in HCM than in DCM (1.78 ± 1.09 vs. 1.23 ± 0.44, p<0.05). PFR was not correlated with cardiac function parameters, such as left ventricular (LV) ejection fraction, cardiac output, LV end-diastolic pressure, LV end-diastolic volume, aortic pressure, or pulmonary artery pressure. However, PFR was significantly correlated with coronary flow in the left anterior descending coronary artery (as evaluated by TIMI frame count) (r(2)=0.3351, p<0.0001, in all-cases combined population), but not with that in the left circumflex or right coronary artery. This correlation remained significant in a logistic regression model tested in 7 variables (body mass index, PVR, CVF, presence of hypertension, dyslipidemia, diabetes mellitus, and atrial fibrillation).
These results indicate that coronary perivascular fibrosis is associated with the impairment of coronary blood flow although not associated with interstitial fibrosis or cardiac function, suggesting that it can be a new therapeutic target to improve coronary microcirculation.
尽管心肌间质纤维化已被认为在慢性心力衰竭（HF）中起致病作用，但另一种纤维化形式——血管周围纤维化的作用仍有待阐明。
我们检查了 2001 年 1 月至 2009 年 4 月在东北大学医院接受心脏导管检查和心内膜心肌活检（右心室间隔侧）诊断为肥厚型心肌病（HCM，n=16）、高血压性心脏病（HHD，n=11）或扩张型心肌病（DCM，n=37）的 64 例非缺血性 HF 连续患者。我们计算了活检样本中的胶原容积分数（CVF）和血管周围纤维化比（PFR），并检查了心肌梗死溶栓（TIMI）帧数以评估冠状动脉血流。
CVF 与 PFR 之间无显著相关性（r²=0.0007）。尽管 HCM、HHD 和 DCM 之间的 CVF 无显著差异（分别为 1.11±1.04、1.89±1.61 和 1.41±1.48），但 HCM 中的 PFR 明显高于 DCM（1.78±1.09 与 1.23±0.44，p<0.05）。PFR 与左心室（LV）射血分数、心输出量、LV 舒张末期压力、LV 舒张末期容积、主动脉压或肺动脉压等心脏功能参数均无相关性。然而，PFR 与左前降支冠状动脉（TIMI 帧数评估）的冠状动脉血流显著相关（在所有病例联合人群中 r²=0.3351，p<0.0001），但与左回旋支或右冠状动脉无关。在 7 个变量（体重指数、PVR、CVF、高血压、血脂异常、糖尿病和心房颤动）的逻辑回归模型中，这种相关性仍然显著。
这些结果表明，尽管与间质纤维化或心功能无关，但冠状动脉血管周围纤维化与冠状动脉血流受损有关，表明它可能是改善冠状动脉微循环的新治疗靶点。
