Chest
Volume 149, Issue 4, April 2016, Pages 900-904
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Commentary
SERVE-HF: More Questions Than Answers

https://doi.org/10.1016/j.chest.2015.12.021Get rights and content

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.

Section snippets

Population Characterization and Protocol Adherence

A critical inclusion criterion was the requirement that enrolled subjects have a documented left ventricular ejection fraction (LVEF) ≤ 45%. However, a range of LVEF values from 9.0% to 71.0% in the control arm and 10.0% to 54.0% in the ASV arm are noted in Table 1 in the article.1 Therefore, a number of patients did not meet the inclusion criteria and had heart failure with preserved ejection fraction (HFpEF). We have been informed, however, that only a small number of patients had HFpEF (oral

Intervention Methodology and Adaptive Servoventilation Issues

The particular ASV device used in SERVE-HF was a first-generation model no longer manufactured by the sponsor. This technology may have applied pressures that were too low for some patients and excessive for others, with adverse cardiovascular consequences. As detailed in a recent publication,7 later generations of ASV devices have incorporated important advances in technology that might have affected the ultimate results had they been used in this trial.

First, the ASV device used in SERVE-HF

Analysis

The study was designed to detect a difference in primary and secondary composite end points that included mortality and readmissions. The statistical design relied on a closed testing method, in which there was no type 1 error control for any outcomes other than the composite primary end point. There was no preplanned analysis or hypothesis testing strategy for mortality in the trial design as was stated in the trial’s design paper6 and the final published trial.1 Consequently, examination of

Acknowledgments

Financial/nonfinancial disclosures: The authors have reported to CHEST the following: S. J. has received honoraria for presentations from Philips Respironics and ResMed Corporation. He is also consultant to Respicardia. L. K. B. serves on the Polysomnography Practice Advisory Committee of the New Mexico Medical Board and chairs the New Mexico Respiratory Care Advisory Board. He has served on a focus group for Koninklijke Philips N.V/Philips Respironics and is a consultant for Considine and

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