Unexplained exertional limitation - Characterization of patients with a mitochondrial myopathy

Exercise intolerance is a common complaint, the cause of which often remain s elusive after a comprehensive evaluation. In this report, we describe 28 patients with unexplained dyspnea or exertional limitation secondary to bio psy-proven mitochondrial myopathies. Patients were prospectively identified from a multidisciplinary dyspnea clinic at a tertiary referral center. All patients were without underlying pulmonary, cardiac, or other neuromuscula r disorders. Patients underwent history, physical examination, complete pul monary function testing, respiratory muscle testing, cardiopulmonary exerci se testing, and muscle biopsy. Results were compared with a group of normal control subjects. The estimated period prevalence was 8.5% (28 of 331). Sp irometry, lung volumes, and gas exchange were normal in patients and contro l subjects. Compared with control subjects, the patient group demonstrated decreased exercise capacity (maximum achieved Vo(2) 67 versus 104% predicte d; p < 0.0001) and respiratory muscle weakness (P-Imax 77 versus 115% predi cted; p = 0.001). These patients have a characteristic exercise response th at was hyperventilatory (peak VE/VCO2; 55 versus 42) and hypercirculatory ( maximum heart rate - baseline heart rate/VO(2)max - baseline VO(2)max; 91 v ersus 41) compared to control subjects. Patients stopping exercise due to d yspnea (n = 16) (as compared with muscle fatigue, n = 11) displayed weaker respiratory muscles (Pdi(max) 61 versus 115 cm H2O; p = 0.01) and were more likely to reach mechanical ventilatory limitation (VEmax/ MVV 0.81 versus 0.58, p = 0.02). The sensation of dyspnea was related to indices of respira tory muscle function including respiratory rate and inspiratory flow. We co nclude that mitochondrial myopathies are more prevalent than previously rep orted. The characteristic physiological profile may be useful in the diagno stic evaluation of mitochondrial myopathy.