06 Dec Cardiovascular Outcomes With Minute Ventilation–Targeted Adaptive Servo-Ventilation Therapy in Heart Failure : The CAT-HF Trial
Adaptive Servo-Ventilation (ASV) is a specific mode of Non-invasive ventilation (NIV) designed to provide respiratory support during central apnoeas or hypoventilation portions of breathing during Cheyne Stokes Respiration (CSR) a form of central sleep apnoea (CSA) which is typically seen in heart failure (HF) patients.
Associated oxygen desaturations during Cheyne Stokes Respiration is common and treatment of this breathing pattern was thought to improve outcomes for suffers by maintaining oxygenation, reducing associated arousals and consolidating sleep.
The SERVE-HF (2015) trial found however there was in fact a negative effect on patient outcomes being increased risk of death and all cause mortality when treated with ASV compared to controls in outpatient population with chronic heart failure, optimized cardiac treatment and a reduced ejection fraction <45%.
Khayat et al (2012) confirmed the presence of CSA during HF hospital admission is associated with an increased risk of mortality including higher rates of rehospitalisation.
This study aimed to assess the effect of ASV treatment in hospitalised heart failure patients on 6 month cardiovascular outcomes.
The most promising aspect was the signal for improved outcomes in a preserved ejection fraction (EF) group. Another study (Yoshihisa et al 2013) reported improvement in symptoms, diastolic function, arterial stiffness and less rehospitalisation for worsening HF when using ASV in HF with preserved ejection fraction.
Methods:
Hospitalised HF patients with either reduced or a preserved ejection fraction and an AHI >15 were randomised to usual care or active treatment. The primary endpoint was a global rank composite endpoint of death, CV hospitalisation and 6-min walk distance (6MWD). Secondary endpoints included changes in functional parameters, biomarkers, QOL, sleep and breathing.
The global rank composite endpoint evaluates a rank order response based on survival time, freedom from CV hospitalization, and improvement in functional capacity measured by change in 6MWD from baseline to 6 months.
Results:
126 patients were randomized 61 to the control group, 65 to the ASV group. The majority of patients had a reduced ejection fraction (EF) <45% and 41% had atrial fibrillation at baseline.
In the ASV group the average device usage at 6 months was only 2.7hrs per day. AHI decreased significantly from baseline in both goups, with a larger decrease in the ASV group (35.7 ± 17.1/h to 2.1 ± 2.2/h) compared with controls (35.1 ± 16.7/h to 19.0 ± 17.1/h).
Primary endpoint:
The primary endpoint comparison was neutral, and there was no significant difference in the global rank endpoint between the ASV and control groups. The results were more favourable in the preserved ejection fraction subgroup (p = 0.036) although this was not statistically significant.
Secondary endpoints:
Patients in the ASV versus control group had statistically significant improvements in disease-specific quality of life (Kansas City Cardiomyopathy Questionnaire score). There were no other statistically significant differences between the groups in terms of number of hospitalisations, all-cause mortality, biomarkers, daytime sleepiness or ECG parameters.
Discussion:
The study was terminated early due to the results of the SERVE-HF trial indicating poorer prognosis for the reduced EF group. As a result the sample size was reduced which limited the statistical power. The ASV usage was also below the recommended 3 hrs noted in the protocol potentially limiting the effect for ASV on the endpoints.
Although the neutral primary endpoint in this population mirrored the main finding of the SERVE-HF trial the studies were different in that the type of sleep apnoea during this study had CSA, OSA or both, whereas the SERVE-HF was limited to CSA. Additionally this study included hospitalised patients with HF regardless of LVEF, whereas the SERVE-HF trial enrolled chronic stable HF patients with reduced EF only.
The most promising aspect was the signal for improved outcomes in the preserved EF group. Another study (Yoshihisa et al 2013) reported improvement in symptoms, diastolic function, arterial stiffness and less rehospitalisation for worsening HF when using ASV in HF with preserved ejection fraction. These hypothesis still need to be validated in a large well control clinical trials however.
Full article http://www.sciencedirect.com/science/article/pii/S0735109717304394