Changes in the Left Ventricular Ejection Fraction and Natriuretic Peptides in Heart Failure Patients with Moderately Reduced and Preserved Ejection Fraction Treated Following Transvenous Stimulation of the Phrenic Nerve for Central Sleep Apnea

Abstract

Introduction Central sleep apnea is a frequent finding in heart failure (HF) and is being increasingly reported in heart failure patients with preserved ejection fraction (HFpEF). Mechanisms of CSA occurrence in those with HFpEF may be similar to CSA in HF with reduced ejection fraction (HFrEF). While treatment of CSA in HFrEF has been reported to be safe and associated with improved sleep metrics, long-term follow-up in patients with moderately reduced ejection fraction (HFmrEF - EF 40-50%) or HFpEF (EF > 50%) and CSA is not well understood. The aim of this analysis was to evaluate changes in LVEF and natriuretic peptides in patients with HFmrEF or HFpEF and CSA following transvenous phrenic nerve stimulation (TPNS). Hypothesis We hypothesized no meaningful reduction in LVEF or increase in natriuretic peptides would be observed. Methods Patients who participated in the remedē system Pivotal trial had TPNS activated 1-month post-implant in the treatment group and 6-months post-implant in the control group. The groups were then pooled for post hoc analysis based on months of active therapy. Echocardiography was performed at 6, 12, and 18 months with attention to EF%, particularly in those without permanent atrial fibrillation, as well as measurement of BNP or NT-pro-BNP at those time points. Results : The HFmrEF group had a median EF of 49.5% [interquartile range (IQR) - 47.0, 53.0] (n=10) at 18 months with a paired change from baseline of 5.0% [2.0, 8.0] (p = 0.031). The HFpEF group had an EF of 56.0% [54.0, 58.0] (n = 10) at 18 months with a paired change from baseline of 1.5% [0.0, 4.0] (p = 0.086). Based on pooled data there was no clinically meaningful change in BNP or NT-pro-BNP over the course of 18 months of active therapy (Table 1). Conclusions This analysis shows no clinically meaningful change in EF based on echocardiographic changes and no clinically meaningful changes in natriuretic peptides following TPNS activation in patients with HFmrEF or HFpEF. Future studies in this patient population should be considered.