Impaired chronotropic response to 6-min walk test and reduced survival in interstitial lung disease

Abstract

Reduced chronotropic response to maximal exercise has been associated with poor survival in people without respiratory disease. The contribution of chronotropic response to exercise limitation and survival in interstitial lung disease (ILD) is not well defined. This study investigated the relationships between chronotropic response during 6-min walk test, exercise capacity and survival in ILD. Eligible participants had ILD, were ambulant and free of heart failure and beta blocker therapy. Chronotropic response during the 6-min walk test was defined as peak heart rate (HR) minus resting HR. Survival was recorded at four years. Sixty-two participants (40 idiopathic pulmonary fibrosis) were included, with mean (SD) TLCO 50(18)% predicted and 6-min walk distance (6MWD) 377 (127) metres. A smaller chronotropic response was associated with reduced 6MWD (r=0.65, p<0.001). Independent predictors of 6MWD were chronotropic response, peak oxygen uptake on cardiopulmonary exercise test; right ventricular systolic pressure on echocardiogram; and age. This model explained 83% of the variance in 6MWD, with 24% of the variance attributable to chronotropic response. A chronotropic response during 6-min walk test of less than 20 beats per minute was an independent predictor of death at four years (odds ratio 10.71, 95% confidence interval 2.67-42.94) in a model that also included oxygen desaturation and forced vital capacity. Impaired chronotropic response to 6-min walk test is associated with reduced 6MWD and reduced survival in ILD, independent of physical fitness and pulmonary hypertension. Investigation of the mechanisms underlying attenuated HR response to exercise in ILD is warranted.