Breathing machines with adaptive servo-ventilation (ASV) did not improve survival or other clinical outcomes in patients with heart failure (HF) and reduced ejection fraction and sleep-disordered breathing, the phase III ADVENT-HF trial found.
Investigators found no difference between patients randomized to standard care plus bilevel positive airway pressure (BiPAP) device therapy with ASV and those getting standard care alone in terms of the combined primary endpoint: all-cause mortality, cardiovascular hospitalization, new-onset atrial fibrillation or flutter, and appropriate implantable cardioverter-defibrillator shock. After an average follow-up of 3.6 years, 166 primary outcome events occurred among the 356 patients in the ASV-treated group as compared with 180 events in the 375 controls (HR 0.95, 95% CI 0.77-1.18).
All-cause mortality by itself was also unchanged with ASV machines (21.3% vs 23.4%, respectively; HR 0.89, 95% CI 0.66-1.21), reported T. Douglas Bradley, MD, of the University Health Network Toronto Rehabilitation Institute, and coauthors in Lancet Respiratory Medicine.
Notably, ADVENT-HF had been prematurely terminated due to a 2021 recall of all Philips positive airway pressure devices, including the ASV devices tested in the trial, the BiPAP autoSV Advanced and BiPAP autoSV Advanced System One. The recall was attributed to identification of disintegration of motor sound-abatement material in affected devices.
In ASV’s defense, Bradley’s group highlighted that the ASV group in ADVENT-HF showed significant improvements in Minnesota Living with Heart Failure Questionnaire scores (average change -2.8, P=0.0009) and Epworth Sleepiness Scale (ESS) scores (-1.0, P<0.0001). These patient-reported improvements were consistent across obstructive sleep apnea (OSA) and central sleep apnea (CSA) subgroups in the open-label trial.
Additionally, study authors considered OSA and CSA eliminated with ASV.
“These novel findings argue that there might be a role for selective application of the ASV treatment strategy used herein as adjunctive therapy for patients with heart failure and reduced ejection fraction and sleep-disordered breathing, including CSA, to reduce symptom burden,” the group concluded.
Unlike the SERVE-HF trial of ASV in patients with HF and reduced ejection fraction and CSA, ADVENT-HF did not show that the treatment increased mortality. Ultimately, no safety issues were identified with ASV treatment in this trial.
Atul Malhotra, MD, of the University of California San Diego in La Jolla, and colleagues noted in an accompanying editorial that many questions remain regarding treatment of sleep-disordered breathing among patients with congestive HF, including which patients should be prioritized for study and whether newer pharmacological agents should be considered to help breathing.
“In theory, positive airway pressure can decrease both preload and afterload, which could have benefits for patients with congestive heart failure,” the editorialists wrote. “However, reducing preload in hypovolemic patients who have received guideline-directed medical therapy for congestive heart failure might compromise cardiac output following aggressive diuresis.”
“Notably, once medical therapy for patients with congestive heart failure has been optimized, treating sleep-disordered breathing might be one of the few therapeutic targets for additional symptomatic benefit,” according to Malhotra and colleagues.
ADVENT-HF was conducted at a total of 49 hospitals across nine countries. Bradley and colleagues had 1,127 patients screened and ended up with 731 participants assigned to receive standard treatment with or without added ASV therapy.
The participant population was over 85% men, and average patient age was in the early 60s. Overall, participants had only mild daytime sleepiness given a mean ESS score of 6.2. Patients were classified as 73% predominantly OSA and 27% predominantly CSA.
Predominantly OSA patients with excessive daytime sleepiness (an ESS score of greater than 10) were excluded from the study on ethical grounds.
Bradley’s group acknowledged that adherence to ASV averaged just 3.8 hours per day at 5 years, with 23% of the assigned ASV group never initiating it or discontinuing it at some point during the study.
Researchers also cautioned that trial enrollment was interrupted on several occasions as a result of the negative SERVE-HF trial being published, the COVID-19 pandemic, and the Philips device recall.
This trial was supported by partial funding from Philips RS North America.
Bradley reported a relationship with Philips.
Malhotra reported relationships with the National Institutes of Health, LivaNova, Zoll, Jazz, Eli Lilly, and ResMed. A co-editorialist reported relationships with Bayer Pharmaceuticals, Philips Respironics, Sommetrics, Apnimed, NovaResp Technologies, and Powell Mansfield.
The Lancet Respiratory Medicine
Source Reference: Bradley TD, et al “Adaptive servo-ventilation for sleep-disordered breathing in patients with heart failure with reduced ejection fraction (ADVENT-HF): a multicentre, multinational, parallel-group, open-label, phase 3 randomised controlled trial” Lancet Respir Med 2023; DOI: 10.1016/S2213-2600(23)00374-0.
The Lancet Respiratory Medicine
Source Reference: Patel SR, et al “Sleep apnoea in congestive heart failure: one step forwards” Lancet Respir Med 2023; DOI: 10.1016/S2213-2600(23)00377-6.