The Hyperkinetic Circulatory Response during Exercise in Metabolic Myopathies: A Peculiar Model of Integrated Biology

A hyperkinetic circulatory response has been described in some metabolic myopathies, a heterogeneous group of inborn errors of intermediary metabolism that interfere with the generation of ATP in skeletal muscle. However, an accurate picture of the cardiovascular response to exercise in the various metabolic myopathies remains elusive.

We therefore sought to systematically review the literature by searching the PubMed/MEDLINE and Embase databases. A meta-analysis was performed from observational studies that evaluated the cardiac output ( Q ), oxygen arteriovenous difference (avDO 2 ), relationship between Q increase and V̇O 2 increase (Δ Q /ΔV̇O 2 ), and peak oxygen uptake (V̇O 2peak ) during a cardiopulmonary exercise testing in patients with metabolic myopathies. A random-effects meta-analysis model was then applied.

From an initial 13,276 literature records, we identified 31 studies fulfilling the inclusion criteria. Compared with healthy age- and sex-matched controls, peak exercise Q is lower in respiratory chain deficiencies (RCD) (standardized mean difference (SMD), -0.63; 95% confidence interval (CI), -1.18 to -0.08) and glycolysis defects (GLY; myophosphorylase defect-McArdle disease, and phosphofructokinase defect-Tarui disease; SMD, -0.76; 95% CI, -1.17 to -0.36), peak exercise avDO 2 is lower in RCD (SMD, -2.28; 95% CI, -3.19 to -1.36) and GLY (SMD, -4.41; 95% CI, -5.81 to -3.02), and Δ Q /ΔV̇O 2 is higher in RCD (SMD, 1.70; 95% CI, 0.91 to 2.48) and GLY (SMD, 3.05; 95% CI, 1.94 to 4.16). Data are limited in lipid oxidation defects, with only two studies showing no difference in the aforementioned variables compared with healthy control subjects.

Although exercise responses were similar between GLY and RCD groups, greater heterogeneity in RCD suggests variable pathophysiology and underscores the need for standardized studies across metabolic myopathies.