Key Project Outcome
This is a double-blinded, sham-controlled, randomized controlled therapy crossover trial evaluating cardiovascular outcomes in patients with obstructive sleep apnea (OSA) using hypoglossal nerve stimulation (HGNS) therapy. This award aimed to answer the question of whether therapeutic levels of HGNS improve brachial artery dilation (FMD). Several studies have shown that endothelial dysfunction is an early hallmark that contributes to cardiovascular disease, and FMD remains the gold-standard method of measuring endothelial function. This aim may elucidate and address a knowledge gap of whether repetitive, neuromuscular excitation of the upper airway during sleep – HGNS therapy – produces substantial improvement in the vascular dysfunction strongly associated with moderate-severe OSA in adult patients.
FMD measures were successfully captured on 40 patients. Our hypothesis was therapeutic levels of HGNS will improve brachial artery dilation while withdrawal of HGNS will result in a return to baseline levels. There was no significant difference in FMD percent change from baseline between “active” and “sham” HGNS (6.44% [4.12] vs. 6.61% [4.98]). Due to COVID-19 pandemic-related resource constraints, our research team was unable to continue performing and capturing pulse wave velocity.
This work is significant to the field as this study is the first major trial design of its kind to assess cardiovascular outcomes in patients who have been surgically-implanted with a HGNS device. In regards to vascular outcomes (i.e. flow-mediated dilation), the trial results did not demonstrate a meaningful difference between the two intervention arms. Though the study was designed to be sham-controlled, our research team found that “sham” therapy more closely represented “sub-therapeutic” HGNS levels. We will use our experience from this novel HGNS trial to inform future trials and their design in studying cardiovascular, neurocognitive and other meaningful outcomes.
Cardiovascular endpoints for obstructive sleep apnea with twelfth cranial nerve stimulation (CARDIOSA-12): Rationale and methods