Muscle Ergoreceptor Overactivity Reflects Deterioration in Clinical Status and Cardiorespiratory Reflex Control in Chronic Heart Failure

Abstract: Background In chronic heart failure (CHF), overactivation of ergoreceptors (afferents sensitive to the metabolic effects of muscular work) may be a link between peripheral changes, sympathetic overactivation, and increased hemodynamic and ventilatory responses to exercise. The relationship between ergoreceptors, autonomic changes, and the progression of the syndrome has not yet been studied. Methods and Results Thirty-eight stable CHF patients (age, 57±1 years; ejection fraction, 26±2%) were compared with 12 age-matched normal control subjects. The ergoreflex contribution to the ventilatory and hemodynamic responses to exercise, together with peripheral and central chemoreceptor sensitivity, arterial baroreflex sensitivity, plasma norepinephrine, epinephrine, and heart rate variability, were measured. Enhanced ergoreflex effects on ventilation (78±2% versus 50±8%), peripheral chemosensitivity (0.6±0.4 versus 0.2±0.1 L/min per percent Sa o 2 ), and central chemosensitivity (2.9±0.2 versus 2.0±0.2 L · min −1 · mm Hg −1 ) and an impaired baroreflex function (4.1±0.6 versus 9.1±5.6 ms/mm Hg) were confirmed in CHF compared with control subjects ( P <0.01 in all comparisons). Ergoreceptor overactivity was associated with a worse symptomatic state (NYHA class, P <0.05), lower exercise tolerance (peak V o 2 , P <0.05), and pronounced exercise hyperventilation (V̇ e /V co 2 , P <0.01). It was also a strong predictor of increased central chemosensitivity (independently of clinical parameters), baroreflex impairment, and sympathetic activation (plasma catecholamines and heart rate variability indexes; all P <0.05). In multivariate analysis, among all reflexes studied, the ventilatory component of the ergoreflex was the only independent predictor of peak V o 2 and V̇ e /V co 2 . Conclusions In CHF, overactivation of the ergoreflex is associated with abnormal cardiorespiratory reflex control, independently of clinical severity. Among impaired reflexes, overactivation of the ergoreflex is an important determinant of exercise hyperventilation and reduced exercise tolerance.