Right ventricular (RV) function is a predictor of outcomes in pulmonary arterial hypertension (PAH). The 6-minute walk test (6MWT) is likely an indirect measure of RV function during exercise, but changes in absolute walk distance can also be influenced by factors like effort and musculoskeletal disease. Paired 6MWT with continuous electrocardiogram monitoring were performed in stable PAH patients, patients adding PAH therapies, and healthy controls. Heart rate expenditure (HRE) was calculated (integrating pulse during 6MWT) and then divided by walk distance (HRE/d). We also evaluated changes in peak heart rate, time above age adjusted maximum predicted heart rate, and heart rate at 6 minutes. HRE/d was compared to invasive hemodynamic measures in patients who had right heart catheterization performed within seven days, WHO functional class assessment, and Emphasis 10 questionnaire. We measured two 6MWT in 15 stable PAH patients, 13 treatment intensification patients, and 8 healthy controls. HRE/d was reproducible in the stable PAH group (median difference, -0.79%), while it decreased (median difference, 23%, p =0.0001) after adding vasodilator therapy. In 11 patients with right heart catheterization, HRE/d correlated strongly with stroke volume, r=-0.72, p=0.01. Peak heart rate decreased after adding vasodilator therapy. HRE/d also correlated with WHO functional class and Emphasis 10 score. Continuous heart rate monitoring during 6MWT provides valuable physiologic data accounting for effort. HRE/d appears to enhance test reproducibility in stable patients while detecting change after adding therapy as compared to walk distance alone.

Introduction Right ventricular (RV) function is an important prognostic indicator in pulmonary arterial hypertension (PAH). Because stroke volume does not usually increase in PAH, heart rate changes during exercise may indirectly reflect RV function. We recently showed that heart rate expenditure (HRE) during 6MW measured by wrist photoplethysmography correlated well with resting RV function. Findings were limited by the data loss associated with photoplethysmography. We therefore evaluated continuous chest electrocardiogram (ECG) recording during the 6-minute walk test (6MWT) to measure changes in HRE divided by walk distance after adding therapy. Methods: We enrolled 24 participants with PAH (5 requiring treatment intensification with repeat walks, 7 stable participants with repeat walks, and 12 participants with one only walk) and 4 healthy controls with repeat walks. In the treatment intensification group, walks were performed at baseline and again 2-3 months later. In stable participants, walks were repeated within 1 month to ensure stability and reproducibility. Continuous ECG heart rate was measured using MC10 Biostamp nPoint. Heart rate was calculated using LabChart 8. HRE/d was calculated by integrating the heart rate over the total time and then dividing by walk distance (meters). Results: In the treatment intensification group, 4 were treatment naïve beginning combination therapy, 4 were females, and median age was 66 years old. In the stable PAH group, median age was 49, 3/7 were females, and 3 were on dual combination therapy only while another 3 were on triple therapy. The median age for the healthy controls was 50 and 3/4 were females. Heart rate expenditure (HRE/d) was calculated for all walks. We found healthy controls had a much lower HRE/d compared to PAH patients, 17.5 beats/m vs. 34 beats/m, p<0.0001 (figure A). After adding therapy, there was a significant decrease in HRE/d, p<0.001 (figure B). The reproducibility of this measure was impressive for those not changing (Figure, C and D). HRE/d had a very strong correlation with functional class (r=0.73, p<0.001). The Biostamp technology adds significantly to the assessment: there was on average a difference of 22 beats/min measured by ECG compared to finger pulse oximetry at the end of the walk. Conclusion: Measuring continuous heart rate during 6MW provides physiologic data about submaximal exercise capacity. It may allow for inexpensive risk stratification among those with longer walks, probably controls for musculoskeletal pain and other confounders, and could be more sensitive at detecting clinical improvement compared to walk distance alone.