Classifying hypopneas as obstructive or central can enhance transvenous phrenic nerve stimulation therapy patient selection and outcomes

Abstract

Study objectives: While not all sleep laboratories distinguish between obstructive and central hypopneas, recent research suggests that patients may receive an incorrect primary diagnosis without this effort. The remedē System Pivotal Trial studied transvenous phrenic nerve stimulation in patients with moderate-to-severe central sleep apnea. Entry criteria required apnea-hypopnea index (AHI) ≥ 20 events/h with central apnea index greater than obstructive apnea index and obstructive apneas < 20% of AHI but did not classify hypopneas. This analysis re-examined sleep studies from the trial to assess hypopnea classification impact on candidacy and treatment outcomes.

Methods: Hypopneas were classified as central vs obstructive by a sleep core laboratory following a modified version of American Academy of Sleep Medicine recommended criteria. AHI composition was assessed pre/post treatment.

Results: At baseline, 91% (138/151) of patients had ≥ 50% of events classified as central accounting for hypopnea classification. If all hypopneas were assumed obstructive, only 63% (95/151) would have had ≥ 50% central events. The likelihood of achieving ≥ 50% AHI reduction increased with the percentage of baseline events that were central: responder rates were 37.5% for patients with < 50% central events, incrementally increasing to 76.5% for those with ≥ 90% central events. At 6 months, residual AHI predominantly consisted of obstructive hypopneas. Central events decreased by 89% with treatment (baseline median 32 events/h). Obstructive apneas and hypopneas increased by 2 and 3 events/h, respectively.

Conclusions: Distinguishing central from obstructive hypopneas is required to accurately determine the proportion of central and obstructive breathing events, and is crucial for appropriate therapy selection and managing patient expectations about treatment outcomes.

Clinical trial registration: Registry: ClinicalTrials.gov; Name: Respicardia, Inc. Pivotal Trial of the remede System; URL: https://www.clinicaltrials.gov/study/NCT01816776, Identifier: NCT01816776.

Citation: Dupuy-McCauley K, Schwartz AR, Javaheri S, Germany R, McKane S, Morgenthaler TI. Classifying hypopneas as obstructive or central can enhance transvenous phrenic nerve stimulation therapy patient selection and outcomes. J Clin Sleep Med. 2025;21(12):2113-2120.

Keywords: central hypopnea; central sleep apnea; transvenous phrenic nerve stimulation.

Figure 1. Summary of component medians by group at baseline and 6 months.

The composition of the apnea-hypopnea index is displayed for each randomized group at each visit. In the treatment group, the central events were nearly eliminated with therapy. The composition of the apnea-hypopnea index did not change much in the control group at 6 months.

Figure 2. Breakdown of disordered breathing events by patient in the treatment group at baseline and at 6 months.

The top half of the figure depicts the composition of the apnea-hypopnea index by event type at baseline, illustrating most of the events are central for nearly all patients, however after classification of hypopneas some patients had a large number of obstructive events. The bottom half of the figure depicts the residual event types after 6 months of therapy. The residual events are primarily obstructive apneas and hypopneas, which transvenous phrenic nerve stimulation is not designed to treat. AHI = apnea-hypopnea index.

Figure 3. Impact of percentage of central events at baseline on effectiveness.

The percentage of individuals achieving a 50% or higher reduction in the apnea-hypopnea index from baseline increased with the percentage of AHI that was central at baseline. AHI = apnea-hypopnea index.

Figure 4. Correlation of baseline CAHI and change in CAHI.

There was a high correlation (−0.862) between the baseline CAHI and the change in the CAHI after 6 months of therapy. Only 1 individual had an increase in the CAHI on therapy. CAHI = central apnea-hypopnea index.