Unexplained Exertional Limitation

Abstract

Exercise intolerance is a common complaint, the cause of which often remains elusive after a comprehensive evaluation. In this report, we describe 28 patients with unexplained dyspnea or exertional limitation secondary to biopsy-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 neuromuscular disorders. Patients underwent history, physical examination, complete pulmonary function testing, respiratory muscle testing, cardiopulmonary exercise testing, and muscle biopsy. Results were compared with a group of normal control subjects. The estimated period prevalence was 8.5% (28 of 331). Spirometry, lung volumes, and gas exchange were normal in patients and control subjects. Compared with control subjects, the patient group demonstrated decreased exercise capacity (maximum achieved V O(2) 67 versus 104% predicted; p < 0.0001) and respiratory muscle weakness (PI(max) 77 versus 115% predicted; p = 0.001). These patients have a characteristic exercise response that was hyperventilatory (peak VE/V CO(2); 55 versus 42) and hypercirculatory (maximum heart rate - baseline heart rate/V O(2)max - baseline V O(2)max; 91 versus 41) compared to control subjects. Patients stopping exercise due to dyspnea (n = 16) (as compared with muscle fatigue, n = 11) displayed weaker respiratory muscles (Pdi(max) 61 versus 115 cm H(2)O; p = 0.01) and were more likely to reach mechanical ventilatory limitation (V Emax/ MVV 0.81 versus 0.58; p = 0.02). The sensation of dyspnea was related to indices of respiratory muscle function including respiratory rate and inspiratory flow. We conclude that mitochondrial myopathies are more prevalent than previously reported. The characteristic physiological profile may be useful in the diagnostic evaluation of mitochondrial myopathy.

Patterns of Oxygen Pulse Curve in Response to Incremental Exercise in Patients with Chronic Obstructive Pulmonary Disease – An Observational Study

“…Fifth, muscle extraction of oxygen has been assumed to be predictable or the frequency of abnormal muscle extraction of oxygen is low in the general population and patients with COPD. However, the rate of mitochondrial myopathy has been estimated to be 8.5% in the general population 40 . Sixth, patient’s BMI or body surface area is related to the cardiovascular size 41 and may influence the magnification factors of radiography thereby influencing parallax and measurements in chest radiographs 42 .…”

Physiology of oxygen uptake kinetics: Insights from incremental cardiopulmonary exercise testing in the Study of Health in Pomerania

“…The latter is more commonly seen, especially in the modern era of beta-blockade. Another cause of an elevated slope is mitochondrial myopathies [28] where HRR values above 50 beats/L were found, reflecting the increased dependency of oxygen uptake on heart rate to compensate for reduced oxygen extraction at the muscle.…”

Novel MTND1 mutations cause isolated exercise intolerance, complex I deficiency and increased assembly factor expression

“…Both cases highlight the importance of serum lactate testing in cases of persistent unexplained exertional weakness or dyspnoea. Indeed, mitochondrial disorders are recognized as a common cause of referral for unexplained dyspnoea, with a period prevalence of up to 8.5% [ 25 ].…”