Cardiology Section, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina;
Am J Physiol Heart Circ Physiol. 2014 May;306(9):H1364-70. doi: 10.1152/ajpheart.00004.2014. Epub 2014 Mar 21.
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 O2 consumption (Vo2), 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 Vo2. In HFPEF versus HC patients, peak Vo2 (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 Vo2. In multivariate analyses, type I fibers and the capillary-to-fiber ratio remained significantly related to peak Vo2. 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.
射血分数保留的心力衰竭（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，其病理生理学尚不清楚。为了确定骨骼肌异常是否导致其严重的峰值运动摄氧量（Vo2）降低，我们通过股外侧肌活检和心肺运动测试检查了 22 名年龄较大的 HFPEF 患者（70±7 岁），并与 43 名年龄匹配的健康对照组（HC）进行了比较，以评估肌肉纤维类型分布和毛细血管以及峰值 Vo2。与 HC 患者相比，HFPEF 患者的峰值 Vo2（14.7±2.1 与 22.9±6.6 ml·kg(-1)·min(-1)，P<0.001）和 6 分钟步行距离（454±72 与 573±71 m，P<0.001）降低。与 HC 患者相比，HFPEF 患者的 I 型纤维百分比（39.0±11.4%与 53.7±12.4%，P<0.001）、I 型与 II 型纤维比例（0.72±0.39 与 1.36±0.85，P=0.001）和毛细血管与纤维比例（1.35±0.32 与 2.53±1.37，P=0.006）降低，而 II 型纤维百分比增加（61±11.4%与 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 型纤维比例（r=0.33，P=0.02）和毛细血管与纤维比例（r=0.59，P<0.0001）与峰值 Vo2 呈正相关。在多变量分析中，I 型纤维和毛细血管与纤维比例与峰值 Vo2 仍显著相关。我们得出结论，年龄较大的 HFPEF 患者的骨骼肌存在明显异常，表现为肌肉纤维类型分布的变化，I 型氧化肌纤维减少，毛细血管与纤维比例降低，这可能导致其严重的运动不耐受。这表明在这种难以治疗的疾病中有潜在的新的治疗靶点。
