Exercise Physiology Impairments of Patients With Amyotrophic Lateral Sclerosis: Cardiopulmonary Exercise Testing Findings

Abstract

Background and ObjectiveIn amyotrophic lateral sclerosis (ALS), progressive weakness significantly limits the ability to exercise. However, measurements of the impaired exercise function and their practical value to assess disease progression in ALS are scarce. Cardiopulmonary exercise testing (CPET) is a non-invasive accurate method used to comprehensively quantify exercise physiology in a variety of diseases. This study aimed to evaluate the clinical value of CPET and to explore its association with disease severity and prognosis prediction in ALS.MethodsA total of 319 participants were enrolled in this 3-year prospective study. After strict quality control, 109 patients with ALS and 150 age- and sex-matched healthy controls were included with comprehensive clinical assessment and follow-ups. The incremental ramp protocol for symptom-limited CPET was applied in both groups. The exercise physiology during peak effort exercise was systematically measured, including the overall aerobic capacity of exercise (VO2 peak) and the respective capacity of the exercise-involved organs [cardiac response (heart rate peak—HR peak), ventilatory efficiency (VE/VCO2 slope), breathing economy (VE/VO2 peak), and other relevant parameters]. Disease severity and progression were evaluated using recognized scales. Survival was monitored with regular follow-ups every 6 months.ResultsDecreased exercise capacity (VO2 peak < 16 ml/kg/min) occurred more frequently in patients with ALS than in controls (44.95% vs. 9.33%, p < 0.01). In patients with ALS, the average VO2 peak (16.16 ± 5.43 ml/kg/min) and HR peak [135 (112–153) bpm] were significantly lower (p < 0.01) than in controls [22.26 ± 7.09 ml/kg/min; 148 (135–164) bpm], but the VE/VCO2 slope was significantly higher [28.05 (25.03–32.16) vs. 26.72 (24.37–29.58); p = 0.03]. In patients with ALS, the VO2 peak and HR peak were significantly correlated with disease severity and progression scores (p < 0.05). Survival analyses revealed the VO2 peak and HR peak as protective indicators while the VE/VO2 peak as a detrimental indicator for the prognostic prediction in ALS (HR = 0.839, p = 0.001; HR = 0.967, p < 0.001; HR = 1.137, p = 0.028, respectively).ConclusionOur prospective study quantified the significantly decreased exercise capacity in ALS through non-invasive CPET. The impaired VO2 peak and HR peak closely correlated with disease severity and independently predicted a worse prognosis. Our findings identified the clinical value of CPET as an objective indicator of disease progression in ALS.

Lowered oxidative capacity in spinal muscular atrophy, Jokela type; comparison with mitochondrial muscle disease

“…These findings indicate an increase in ventilation in mitochondrial disease to be excessive and are common in hyperventilation (42,43). In ALS, higher VE/V′O 2 has also been shown to be an indicator of poor prognosis, even if it did not significantly differ from healthy controls (30), but these changes of FetCO 2 and VE/V′O 2 typically related to mitochondrial dysfunction in an exercise test were absent in the SMAJ group in our study.…”

Cardiopulmonary Exercise Testing in Heart Failure

“…Depending on the exact metabolic abnormality in these muscles, these patients may or may not have increased anaerobic metabolism. Some muscular disorders also involve cardiac muscle, and this makes this interpretation more difficult [ 32 , 33 ]. In addition, patients with HF also lose muscle mass, which contributes to their exercise limitation.…”

Rehabilitación basada en ejercicio físico en pacientes con esclerosis lateral amiotrófica

“…Al respecto, Sassani et al 19 demostraron la presencia de disfunción mitocondrial en el músculo esquelético de pacientes con ELA por medio de espectroscopía por resonancia magnética. Además, los estudios basados en pruebas de ejercicio cardiopulmonar han evidenciado la alteración de la fisiología del ejercicio en esta patología y que los sujetos con esta enfermedad presentan un deterioro del metabolismo oxidativo evidenciado por un decremento en el consumo pico de oxígeno (VO 2 pico) y la frecuencia cardiaca pico durante el ejercicio, asociada a un aumento de la producción de lactato en comparación con controles [20][21][22][23] . Por otro lado, la respuesta metabólica de los ácidos grasos al ejercicio prolongado se ha encontrado significativamente retardada en pacientes con ELA 21 .…”