McKane, Scott

Abstract Introduction The remedē System® Therapy Study (reST) is a real world evaluation using transvenous phrenic nerve stimulation (TPNS) to treat adults with moderate-to-severe central sleep apnea (CSA). Based on previous clinical trials, it was expected that most patients with CSA would have heart failure (HF). However, recent CSA prevalence publications demonstrated the opposite. We present the baseline characteristics of patients with CSA treated with TPNS. Methods Adult subjects determined eligible for a commercial TPNS device implant by routine clinical PSGs were consented to participate in the trial. Baseline assessments were performed and medical history collected. Patients will be followed for ≥1 year following therapy activation; follow-up is ongoing. This report describes the baseline characteristics of the patient population. Results Twenty-nine sites enrolled a total of 197 subjects (171 United States & 26 the Netherlands) between July 2019 and March 2025. Median [Q1-Q3] age was 70 [61-76] years, 82% were male, and 97% white race. Body mass index was 28.7 [25.8-31.6] kg/m2, with neck size 41 [28-44] cm. Patients had moderate-to-severe CSA with site-reported apnea-hypopnea index of 46/hour [30-64], including central apnea index of 24/hour [13-38]. Despite a range of comorbidities among patients, HF was documented in just 23%. Other cardiovascular conditions were more prevalent, including hypertension (70%), hyperlipidemia (65%), coronary artery disease (37%), atrial fibrillation (34%), and prior stroke (14%). Non-cardiac issues such as depression (27%), diabetes (26%), and renal disease (18%) were also present. Additionally, 22% of patients used narcotics, and 89% had previously failed another CSA therapy, most often CPAP (79%), Bi-PAP (39%), or ASV (32%). Lastly, almost 20% were from high altitude locations (>5,000 feet). Conclusion Patients implanted with TPNS had significant co-morbidities. However, HF was much less common than anticipated. This finding could be due to CSA being present in clinical practice with a wider range of underlying causes beyond HF, or undiagnosed early-stage HF. Alternatively, it may reflect referral bias for this specific therapy, with patients selected because of prior treatment failures or other comorbidities. These possibilities highlight the importance of recognizing CSA in a diverse patient population and underscore the need for multidisciplinary team management. Support (if any) ZOLL Respicardia, Inc.

Abstract Introduction Despite AASM scoring guidelines encouraging classifying hypopneas as central or obstructive, classification is underutilized in practice. However, without that effort patients may receive an incorrect primary diagnosis and suboptimal treatment. The remedē® System Pivotal Trial studied transvenous phrenic nerve stimulation (TPNS) to treat adult patients with moderate to severe central sleep apnea (CSA). Entry criteria required apnea hypopnea index (AHI)≥20 with the central apnea index (CAI) greater than the obstructive apnea index and obstructive apneas< 20% of AHI but did not consider hypopnea differentiation. This analysis re-examined sleep studies from the trial to assess how hypopnea classification might lead to better patient selection for this therapy. Methods Hypopneas were classified as central versus obstructive by a sleep core laboratory following a modified version of AASM recommended criteria. The AHI composition was assessed at baseline and after 6 months of therapy. Results At baseline, 91% (138/151) of patients had ≥50% of events classified as central when accounting for hypopnea classification. If all hypopneas were assumed to be obstructive, only 63% (95/151) would have had ≥50% central events. Additionally, 95% (144/151) of patients had central AHI ≥15/hour, compared to 73% (110/151) with a central apnea index (CAI) ≥15/hour. The likelihood of achieving a ≥50% AHI reduction increased with the percentage of baseline events that were central: responder rates were 37.5% for patients with < 50% central events at baseline, incrementally increasing to 76.5% for those with ≥90% central events. At 6 months, the residual AHI predominantly consisted of obstructive events. Central events decreased by 89% with treatment, from a baseline median of 32/hour [1st and 3rd quartiles: 22, 50]. Obstructive apneas rose by 2/hour and obstructive hypopneas increased by 2/hour from a baseline median of 5 obstructive events/hour [2, 12]. Conclusion Distinguishing central from obstructive hypopneas is required to accurately determine if a patient has central sleep apnea/Cheyne Stokes respiration, and is crucial for epidemiologic studies, appropriate therapy selection, and managing patient expectations about treatment outcomes. This analysis suggests that accurate hypopnea classification may prevent disqualification of patients who could benefit from TPNS therapy, which effectively treats central sleep apnea syndrome. Support (if any) ZOLL Respicardia, Inc.

Abstract Introduction Adherence with mask-based therapies remains a significant challenge for optimal treatment of patients with sleep disordered breathing. Transvenous phrenic nerve stimulation (TPNS) to treat central sleep apnea offers a novel, automated approach to enhance nightly adherence by initiating therapy based on patient-specific programmed conditions such as sleep schedule, activity, and body position. Therapy automatically pauses when the patient sits up or changes position, facilitating re-initiation of sleep. This research aimed to determine the degree of adherence achieved with TPNS’s automated activation approach. Methods Device data from 128 remedē® System Pivotal Trial participants were analyzed to calculate hours of therapy activation. Daily use from device data within the 14 days prior to scheduled visits were used to calculate median daily hours of therapy per patient, and subsequently the overall median daily use for all patients. Therapy duration was defined as the sum of time of delivered therapy when all conditions to activate therapy were met between the first time therapy came on to the last time off during the night, excluding time when activity or body position did not meet the programmed criteria for therapy activation. Results The median [Q1-Q3] nightly therapy duration at 6, 12, 18, and 24 months was 5.9 [4.9-6.6], 5.7 [5.0-6.8], 6.0 [5.3-6.8], and 5.9 [4.9-6.5] hours, respectively. Using a definition for adequate therapy as the percentage of patients with usage ≥4 hours/night for at least 70% of nights, 86%, 82%, 83%, and 90% of patients met the criteria at these visits. Only two patients (< 2%) who had therapy activated discontinued treatment prior to 6 months due to stimulation intolerance. Patients with median delivered therapy ≥4 hours/night reported more quality of life improvement than patients with < 4 hours of therapy. Conclusion The automatic activation of TPNS therapy resulted in a higher duration of nightly usage and higher rate of adequate delivered therapy than generally are reported for mask-based therapies. This high usage may yield a greater overall reduction in central sleep apnea burden over the whole night compared to therapies that require the patient to initiate the therapy. Support (if any) ZOLL Respicardia, Inc.