000147970 001__ 147970 000147970 005__ 20250113143111.0 000147970 0247_ $$2doi$$a10.1016/S2213-2600(23)00374-0 000147970 0248_ $$2sideral$$a141349 000147970 037__ $$aART-2023-141349 000147970 041__ $$aeng 000147970 100__ $$aBradley, T Douglas 000147970 245__ $$aAdaptive 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 000147970 260__ $$c2023 000147970 5060_ $$aAccess copy available to the general public$$fUnrestricted 000147970 5203_ $$aBackground In patients with heart failure and reduced ejection fraction, sleep-disordered breathing, comprising obstructive sleep apnoea (OSA) and central sleep apnoea (CSA), is associated with increased morbidity, mortality, and sleep disruption. We hypothesised that treating sleep-disordered breathing with a peak-flow triggered adaptive servo-ventilation (ASV) device would improve cardiovascular outcomes in patients with heart failure and reduced ejection fraction. Methods We conducted a multicentre, multinational, parallel-group, open-label, phase 3 randomised controlled trial of peak-flow triggered ASV in patients aged 18 years or older with heart failure and reduced ejection fraction (left ventricular ejection fraction ≤45%) who were stabilised on optimal medical therapy with co-existing sleep-disordered breathing (apnoea-hypopnoea index [AHI] ≥15 events/h of sleep), with concealed allocation and blinded outcome assessments. The trial was carried out at 49 hospitals in nine countries. Sleep-disordered breathing was stratified into predominantly OSA with an Epworth Sleepiness Scale score of 10 or lower or predominantly CSA. Participants were randomly assigned to standard optimal treatment alone or standard optimal treatment with the addition of ASV (1:1), stratified by study site and sleep apnoea type (ie, CSA or OSA), with permuted blocks of sizes 4 and 6 in random order. Clinical evaluations were performed and Minnesota Living with Heart Failure Questionnaire, Epworth Sleepiness Scale, and New York Heart Association class were assessed at months 1, 3, and 6 following randomisation and every 6 months thereafter to a maximum of 5 years. The primary endpoint was the cumulative incidence of the composite of all-cause mortality, first admission to hospital for a cardiovascular reason, new onset atrial fibrillation or flutter, and delivery of an appropriate cardioverter-defibrillator shock. All-cause mortality was a secondary endpoint. Analysis for the primary outcome was done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT01128816 ) and the International Standard Randomised Controlled Trial Number Register (ISRCTN67500535), and the trial is complete. Findings The first and last enrolments were Sept 22, 2010, and March 20, 2021. Enrolments terminated prematurely due to COVID-19-related restrictions. 1127 patients were screened, of whom 731 (65%) patients were randomly assigned to receive standard care (n=375; mean AHI 42·8 events per h of sleep [SD 20·9]) or standard care plus ASV (n=356; 43·3 events per h of sleep [20·5]). Follow-up of all patients ended at the latest on June 15, 2021, when the trial was terminated prematurely due to a recall of the ASV device due to potential disintegration of the motor sound-abatement material. Over the course of the trial, 41 (6%) of participants withdrew consent and 34 (5%) were lost to follow-up. In the ASV group, the mean AHI decreased to 2·8–3·7 events per h over the course of the trial, with associated improvements in sleep quality assessed 1 month following randomisation. Over a mean follow-up period of 3·6 years (SD 1·6), ASV had no effect on the primary composite outcome (180 events in the control group vs 166 in the ASV group; hazard ratio [HR] 0·95, 95% CI 0·77–1·18; p=0·67) or the secondary endpoint of all-cause mortality (88 deaths in the control group vs. 76 in the ASV group; 0·89, 0·66–1·21; p=0·47). For patients with OSA, the HR for all-cause mortality was 1·00 (0·68–1·46; p=0·98) and for CSA was 0·74 (0·44–1·23; p=0·25). No safety issue related to ASV use was identified. Interpretation In patients with heart failure and reduced ejection fraction and sleep-disordered breathing, ASV had no effect on the primary composite outcome or mortality but eliminated sleep-disordered breathing safely. 000147970 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/ 000147970 590__ $$a38.7$$b2023 000147970 591__ $$aCRITICAL CARE MEDICINE$$b1 / 55 = 0.018$$c2023$$dQ1$$eT1 000147970 591__ $$aRESPIRATORY SYSTEM$$b1 / 101 = 0.01$$c2023$$dQ1$$eT1 000147970 592__ $$a7.965$$b2023 000147970 593__ $$aPulmonary and Respiratory Medicine$$c2023$$dQ1 000147970 594__ $$a87.1$$b2023 000147970 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion 000147970 700__ $$aLogan, Alexander G 000147970 700__ $$aLorenzi Filho, Geraldo 000147970 700__ $$aKimoff, R John 000147970 700__ $$aDurán Cantolla, Joaquin 000147970 700__ $$aArzt, Michael 000147970 700__ $$aRedolfi, Stefania 000147970 700__ $$aParati, Gianfranco 000147970 700__ $$aKasai, Takatoshi 000147970 700__ $$aDunlap, Mark E 000147970 700__ $$aDelgado, Diego 000147970 700__ $$aYatsu, Shoichiro 000147970 700__ $$aBertolami, Adriana 000147970 700__ $$aPedrosa, Rodrigo 000147970 700__ $$aTomlinson, George 000147970 700__ $$0(orcid)0000-0001-9096-2294$$aMarin Trigo, Jose M$$uUniversidad de Zaragoza 000147970 700__ $$aTantucci, Claudio 000147970 700__ $$aFloras, John S 000147970 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina 000147970 773__ $$g12, 2 (2023), 153-166$$pThe Lancet. Respir. med.$$tThe Lancet. Respiratory medicine$$x2213-2600 000147970 8564_ $$s1220464$$uhttps://zaguan.unizar.es/record/147970/files/texto_completo.pdf$$yPostprint 000147970 8564_ $$s3050637$$uhttps://zaguan.unizar.es/record/147970/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint 000147970 909CO $$ooai:zaguan.unizar.es:147970$$particulos$$pdriver 000147970 951__ $$a2025-01-13-14:30:29 000147970 980__ $$aARTICLE