Neurophysiological mechanisms of exertional dyspnea in post-pulmonary embolism syndrome.

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 CO (V̇e/V̇co), and perceived dyspnea intensity (modified Borg 0-10 scale). Post-PE (vs. control) had a reduced resting transfer coefficient for carbon monoxide (: 84 ± 15 vs. 104 ± 14%pred, < 0.001) and peak oxygen uptake (V̇o) (76 ± 14 vs. 124 ± 28%pred, < 0.001). IND and V̇e/V̇co were higher in post-PE than controls at standardized submaximal work rates ( < 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 ( < 0.05). High IND was associated with low ( = -0.484, < 0.001), high V̇e/V̇co nadir ( = 0.453, < 0.001), and low V̇o ( = -0.523, < 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 and high exercise V̇e/V̇co, which suggest important pulmonary gas-exchange abnormalities in this patient population. This study is the first to show that increased exertional dyspnea in patients with post-pulmonary embolism (PE) syndrome, without overt pulmonary hypertension, was strongly associated with elevated inspiratory neural drive (IND) to the diaphragm during exercise, compared with healthy controls. The greater IND was associated with impairments in pulmonary gas exchange and significant deconditioning. Our results help to explain why many patients with post-PE syndrome report significant dyspnea at relatively low levels of physical activity.