Skeletal muscle abnormalities and exercise intolerance in older patients with heart failure and preserved ejection fraction
Skeletal muscle abnormalities and exercise intolerance in older patients with heart failure and preserved ejection fraction
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DOI：
10.1152/ajpheart.00004.2014
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发表时间：
2014-05-01
影响因子：
4.8
通讯作者：
Haykowsky, Mark
中科院分区：
文献类型：
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作者：
Kitzman, Dalane W.;Nicklas, Barbara;Haykowsky, Mark
射血分数保留性心力衰竭（HFPEF）是老年人中最常见的心力衰竭形式。HFPEF的主要慢性症状是严重的运动不耐受，其病理生理机制知之甚少。为了确定骨骼肌异常是否导致运动耗氧量峰值（Vo（2））严重降低，我们检查了22名老年HFPEF患者（70 ± 7岁）和43名年龄匹配的健康对照（HC）受试者，采用股外侧肌穿刺活检和心肺运动试验评估肌纤维类型分布和毛细作用以及峰值Vo（2）。HFPEF患者与HC患者相比，峰值Vo（2）（14.7 +/- 2.1 vs. 22.9 +/- 6.6 ml.kg（-1）min（-1），P < 0.001）和6分钟步行距离（454 +/- 72 vs. 573 +/- 71 m，P < 0.001）减少。在HFPEF与HC患者中，I型纤维的百分比（39.0 +/- 11.4% vs. 53.7 +/-12.4%，P < 0.001），I型与II型纤维比率（0.72 +/- 0.39 vs. 1.36 +/- 0.85，P < 0.001），毛细血管-纤维比率（1.35 +/- 0.32 vs. 2.53 +/- 1.37，P = 0.006）减少，而II型纤维的百分比更大（61 ± 11.4% vs. 46.3 ± 12.4%，P < 0.001）。在单变量分析中，I型纤维百分比（r = 0.39，P = 0.003）、I型与II型纤维比率（r = 0.33，P = 0.02）和毛细血管与纤维比率（r = 0.59，P < 0.0001）与峰值Vo（2）呈正相关。在多变量分析中，I型纤维和毛细血管-纤维比与Vo峰值显著相关（2）。我们的结论是，老年HFPEF患者有显着的骨骼肌异常，其特点是肌纤维类型分布的转变，减少I型氧化肌纤维和减少毛细血管纤维比，这些可能有助于他们严重的运动不耐受。这表明在这种难以治疗的疾病中有潜在的新治疗靶点。
Heart failure (HF) with preserved ejection fraction (HFPEF) is the most common form of HF in older persons. The primary chronic symptom in HFPEF is severe exercise intolerance, and its pathophysiology is poorly understood. To determine whether skeletal muscle abnormalities contribute to their severely reduced peak exercise O-2 consumption (Vo(2)), we examined 22 older HFPEF patients (70 +/- 7 yr) compared with 43 age-matched healthy control (HC) subjects using needle biopsy of the vastus lateralis muscle and cardiopulmonary exercise testing to assess muscle fiber type distribution and capillarity and peak Vo(2). In HFPEF versus HC patients, peak Vo(2) (14.7 +/- 2.1 vs. 22.9 +/- 6.6 ml.kg(-1) min(-1), P < 0.001) and 6-min walk distance (454 +/- 72 vs. 573 +/- 71 m, P < 0.001) were reduced. In HFPEF versus HC patients, the percentage of type I fibers (39.0 +/- 11.4% vs. 53.7 +/- 12.4%, P < 0.001), type I-to-type II fiber ratio (0.72 +/- 0.39 vs. 1.36 +/- 0.85, P < 0.001), and capillary-to-fiber ratio (1.35 +/- 0.32 vs. 2.53 +/- 1.37, P = 0.006) were reduced, whereas the percentage of type II fibers was greater (61 +/- 11.4% vs. 46.3 +/- 12.4%, P < 0.001). In univariate analyses, the percentage of type I fibers (r = 0.39, P = 0.003), type I-to-type II fiber ratio (r = 0.33, P = 0.02), and capillary-to-fiber ratio (r = 0.59, P < 0.0001) were positively related to peak Vo(2). In multivariate analyses, type I fibers and the capillary-to-fiber ratio remained significantly related to peak Vo(2). We conclude that older HFPEF patients have significant abnormalities in skeletal muscle, characterized by a shift in muscle fiber type distribution with reduced type I oxidative muscle fibers and a reduced capillary-to-fiber ratio, and these may contribute to their severe exercise intolerance. This suggests potential new therapeutic targets in this difficult to treat disorder.