SERVE-HF: More Questions Than Answers

Abstract

The recent online publication of the SERVE-HF trial that evaluated the effect of treating central sleep apnea (CSA) with an adaptive servoventilation (ASV) device in patients with heart failure and reduced ejection fraction (HFrEF) has raised serious concerns about the safety of ASV in these patients. Not only was ASV ineffective but post hoc analysis found excess cardiovascular mortality in treated patients. The authors cited as one explanation an unfounded notion that CSA is a compensatory mechanism with a protective effect in HFrEF patients. We believe that there are several possible considerations that are more likely to explain the results of SERVE-HF. In this commentary, we consider methodological issues including the use of a previous-generation ASV device that constrained therapeutic settings to choices that are no longer in wide clinical use. Patient selection, data collection, and treatment adherence as well as group crossovers were not discussed in the trial as potential confounding factors. We have developed alternative reasons that could potentially explain the results and that can be explored by post hoc analysis of the SERVE-HF data. We believe that our analysis is of critical value to the field and of particular importance to clinicians treating these patients.

Impact of sacubitril–valsartan combination in patients with chronic heart failure and sleep apnoea syndrome: the ENTRESTO‐SAS study design

“…In the context of the SERVE‐HF study,23 a trial that has raised serious concerns about the effect of adaptative servoventilation in patients with HFrEF and CSA, physicians are waiting for new trials and alternative therapies. Because of its reported beneficial effects and its mechanism of action, we believe that sacubitril–valsartan needs to be evaluated 25.…”

Sleep-Disordered Breathing in Heart Failure ― A Therapeutic Dilemma ―

“…74- 80 It was noted that a number of individuals with HFpEF slipped into this trial. In the majority of trial participants it was home polygraphy that was used to diagnose CSA.…”

“…The predominant use of a full face rather than a nasal mask may have compromised adherence, which was, on average, only 3.7 h/night and also encouraged CO2 rebreathing. 80 A second hypothesis is that by inducing hyperventilation the mv-ASV algorithm might have created an enhanced metabolic substrate for ventricular arrhythmias.…”

“…The initial trial design was predicated on the occurrence of 651 events in 1,193 patients, but for logistical tissue perfusion and increasing lung-chemoreceptor circulatory delay. 80 The SERVE-HF protocol called for use of a full face mask when initiating ASV. During chronic therapy 76% reported as continuing on a full face and 15% on a nasal mask (with 9% unknown).…”

Keep Calm and Debate On

“…Johnson and Johnson to "Updated Adaptive Servo-Ventilation (ASV) Recommendations for the 2012 AASM Guideline." 1 The concerns that they raise, along with other commentaries 2,3 in response to Cowie et al 4 are reminiscent of the controversy following the publication of the CanPAP study in 2005. 5 The SERVE-HF study was a large randomized controlled trial utilizing intention to treat analysis which found that ASV had no impact on the primary endpoints (the first event of lifesaving cardiovascular intervention, unplanned hospitalization for worsening heart failure, or death from any cause).…”