Skeletal muscle abnormalities and exercise intolerance in older patients with heart failure and preserved ejection fraction

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.