Effects of Adaptive Servo-Ventilation in Heart Failure Patients with preserved Ejection Fraction and Central Sleep Apnea on Nocturnal Blood Pressure (VENT-HF I Blood Pressure) - A Multicenter Randomized Cross-Over Withdrawal Trial

• Applicant: Professor Dr. Michael Arzt
• Subject Area: Pneumology, Thoracic Surgery ; Cardiology, Angiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 523926807

Rationale: In Europe heart failure with preserved ejection fraction (HFpEF) leads to 0.5 million hospitalizations per year. Treatment options to reduce morbidity and mortality in patients with HFpEF are currently scarce. Therefore, attention has been directed towards co-morbidities of HFpEF and to interventions aimed at improving quality of life. A promising common co-morbidity to treat in patients with HFpEF is central sleep apnea (CSA). Treatment of CSA in patients with HFpEF may provide an opportunity to prevent progression of HFpEF via reduction in (nocturnal) arterial blood pressure and cardiac workload, as well as prevention of cardiac remodeling as well as improvement of quality of life. Previous pilot data on positive airway pressure in patients with HFpEF and CSA are promising, but lack sufficient power to show a significant effect on (nocturnal) arterial blood pressure and cardiac biomarkers. Therefore, the objectives of the proposed trial are to test the hypothesis that a withdrawal of Adaptive Servo-Ventilation (ASV) for 2 weeks leads to a >=3 mmHg rise of mean nocturnal blood pressure, an increase in heart rate and biomarkers for the severity HFpEF as well as and an impairment of general as well as disease specific quality of life. Methods: To test these hypothesis, we will perform a randomized, cross-over, multicenter, withdrawal trial of ASV. Key inclusion criteria are HFpEF and an established therapy with ASV for CSA in clinical routine. Outcomes will be assessed after 2 weeks and compared with the assessments after a 2 week control period on effective ASV. The "withdrawal trial" design for a treatment period of 2 weeks is ethical and established to study short-term outcomes of positive airway pressure therapy in obstructive sleep apnea including blood pressure. Feasibility: To detect a clinically relevant mean difference of 3 mmHg in mean nocturnal blood pressure between continued ASV therapy and withdrawn ASV therapy a total of 90 patients is required for statistical analyses. Ten experienced study sites were identified for participation using a site feasibility checklist. Sites can plausibly randomize the required number of eligible patients within 24 months. Novelty, patient benefit and clinical impact: The proposed confirmatory trial will provide novel evidence, whether positive airway pressure treatment of CSA in patients with HFpEF reduces mean nocturnal blood pressure and whether treatment of CSA as well as a reduction of nocturnal blood pressure will translate into a reduction of biomarkers for the severity of HFpEF and quality of life. International guidelines have pointed out that the proposed effect size of 3 mmHg change in nocturnal arterial blood pressure could cause a significant reduction in cardiovascular mortality. In contrast to pharmacological antihypertensive treatments, ASV has the potential to directly improve quality of life via reversal of sleep fragmentation and intermittent hypoxia.

• DFG Programme: Clinical Trials
• Co-Investigators: Professor Dr. Stefan Wagner; Dr. Michael Wester