Neurophysiological mechanisms of exertional dyspnea in post-pulmonary embolism syndrome

Abstract

Following pulmonary embolism (PE), a third of patients develop persistent dyspnea, which is commonly termed the post-PE syndrome. The neurophysiological underpinnings of exertional dyspnea in patients with post-PE syndrome without pulmonary hypertension (PH) are unclear. Thus, the current study determined if abnormally high inspiratory neural drive (IND) due, in part, to residual pulmonary gas-exchange abnormalities, was linked to heightened exertional dyspnea and exercise limitation, in such patients. Fourteen participants with post-PE syndrome (without resting PH) and 14 age- sex- and body mass index-matched healthy controls undertook pulmonary function testing and a symptom-limited cycle cardiopulmonary exercise test with measurements of IND (diaphragmatic electromyography), ventilatory requirements for CO2 (V̇E/V̇CO2), and perceived dyspnea intensity (modified Borg 0-10 scale). Post-PE (vs control) had a reduced resting transfer coefficient for carbon monoxide (KCO: 84±15 vs 104±14%pred, p<0.001) and peak oxygen uptake (V̇O2peak)(76±14 vs 124±28%pred, p<0.001). IND and V̇E/V̇CO2 were higher in post-PE than controls at standardized submaximal work rates (p<0.05). Dyspnea increased similarly in both groups as a function of increasing IND but was higher in post-PE at standardized submaximal work rates (p<0.05). High IND was associated with low KCO (r=-0.484, p<0.001), high V̇E/V̇CO2 nadir (r=0.453, p<0.001) and low V̇O2peak (r=-0.523, p<0.001). In patients with post-PE syndrome, exercise IND was higher than controls and was associated with greater dyspnea intensity. The heightened IND and dyspnea in post-PE, in turn, were strongly associated with low resting KCO and high exercise V̇E/V̇CO2, which suggest important pulmonary gas-exchange abnormalities in this patient population.