Supplementary Material for: Respiratory Sinus Arrhythmia Attenuation via Targeted Lung Denervation in Sheep and Humans

Background: Targeted lung denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung. Parasympathetic input to the heart originating from the lungs contributes to respiratory sinus arrhythmia (RSA) and disruption of pulmonary nerves via TLD may impact RSA. Objective: The aim of this study was to assess the potential of TLD to affect RSA in sheep and humans. Methods: TLD was performed in 5 sheep and 9 humans using a novel lung denervation system (Nu­vaira Inc., Minneapolis, MN, USA) with an electrocardiogram collected before and after the procedure. Frequency domain analysis of heart rate variability was performed in 5 sheep and 6 humans with presence of RSA approximated as high-frequency power (HF power). Results: HF power decreased in 3 of 5 sheep with 1 animal reaching less than 7% of its baseline HF power 30 days after TLD. The average treatment location was more distal in the remaining 2 animals, which did not exhibit RSA attenuation, suggesting diminished denervation. HF power decreased in 5 of 6 humans, with 3 subjects reaching less than 50% of their baseline HF power 90 days after TLD. Conclusions: TLD appeared to attenuate RSA in both sheep and human cohorts of this sub-study. Further confirmation in humans is necessary to allow for RSA attenuation to be used as a marker of successful lung denervation via TLD.