To the Editor:
The SERVE-HF trial (Treatment of Predominant Central Sleep Apnoea by Adaptive Servo Ventilation in Patients With Heart Failure) commentary by Yogasundaram and Oudit contains a factual error and several misconceptions that could discourage others from initiating or completing other trials such as the ADVENT-HF trial (A Multi-Centre Randomized Study to Assess the Effects of Adaptive Servo Ventilation on Survival and Frequency of Cardiovascular Hospital Admissions in Patients with Heart Failure and Sleep Apnea) of adaptive servo-ventilation (ASV) for the treatment of central sleep apnea (CSA) and obstructive sleep apnea (OSA) in heart failure (HF) that involve different devices.
1
First, the title is incorrect. The SERVE-HF trial was not “halted.” It concluded, per protocol, when the goal of 651 observed events was achieved.
2
Second, the SERVE-HF publication reports only the results of a treatment strategy.2
Yet to be disclosed is whether the actual use of ASV was associated with an excess of cardiovascular deaths.Importantly, 16% of patients allocated to the control group crossed over to positive airway pressure devices during the trial, whereas approximately 29% of patients allocated to ASV abandoned it.
2
Compliance was poor, averaging only 3.4 hours/night 1 year after randomization, perhaps because a full face mask, which is less well tolerated than a nasal mask,3
was used by 76% of the treated participants.2
A second possibility is that the SERVE-HF device's relatively high default pressures (minimum end-expiratory pressure of 5 cm H2O and minimum inspiratory pressure support of 3 cm H2O) are more likely to induce hyperventilation and to lower cardiac output in participants with normal or low left ventricular filling pressures than ASV using lower default pressures.The commentators' recommendation that “HF patients with CSA who are optimally treated medically and with device therapy but remain symptomatic should be given a trial of continuous positive airway therapy without ASV” is unsubstantiated by current evidence.
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The SERVE-HF investigators note that algorithms used by different ASV devices vary and acknowledge that the ADVENT-HF trial “may help determine whether the safety signal identified in SERVE-HF is limited to a particular device or algorithm.”2
In their editorial, Magalang and Pack also refer to the difference between the SERVE-HF and the ADVENT-HF ASV algorithms and recommend that until “other studies clarify whether the results seen in the SERVE-HF trial are a consequence of the specific device that was used, that adaptive servo-ventilation not be used outside clinical trials in patients with heart failure who have predominantly central sleep apnea.”4
We endorse these recommendations and encourage those contemplating treatment of patients with HF and CSA (and also patients with asymptomatic OSA) to consider referring them to an ADVENT-HF trial centre.As advocated,
1
the use of ASV is carefully monitored in the ADVENT-HF trial. From its inception, ADVENT-HF incorporated more stringent safety features than, and differs from, SERVE-HF in several key respects: all ASV titrations are reviewed centrally, device pressure settings are prescribed by the core sleep laboratory to maintain the lowest pressures possible, follow-up is at 6-month intervals vs yearly in SERVE-HF, and the Data Safety and Monitoring Committee (DSMC) reviews data every 6 months compared with only twice over the 7-year course of SERVE-HF. Compared with SERVE-HF, in ADVENT-HF the ASV administered has lower default end-expiratory and pressure support settings (4 and 0 cm H2O, respectively), a much higher proportion (78%) of participants randomized to ASV are wearing a nasal mask, and present nightly average ASV use is more than an hour greater.After the release of the SERVE-HF results, the ADVENT-HF DSMC reviewed all adjudicated events separately for patients randomized on the basis of CSA and OSA and recommended that the trial be conducted without modification.
Disclosures
Dr Bradley is Chair and Drs Floras and Logan are Vice-Chairs of the ADVENT-HF trial, which is funded by a Canadian Institutes of Health Research/SME Grant (IS2-05225) and an unrestricted gift to the Toronto Rehabilitation Institute from Philips Respironics Inc.
References
- Increased mortality associated with adaptive servo-ventilation therapy in heart failure patients with central sleep apnea in the halted SERVE-HF trial.Can J Cardiol. 2015; 31: 1202-1203
- Adaptive servo-ventilation for central sleep apnea in systolic heart failure.N Engl J Med. 2015; 373: 1095-1105
- Comparison of nose and face mask CPAP therapy for sleep apnoea.Thorax. 1998; 53: 290-292
- Heart failure and sleep-disordered breathing—the plot thickens.N Engl J Med. 2015; 373: 1166-1167
Article info
Publication history
Published online: October 13, 2015
Identification
Copyright
© 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
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Access this article on ScienceDirectLinked Article
- Increased Mortality Associated With Adaptive Servo-Ventilation Therapy in Heart Failure Patients With Central Sleep Apnea in the Halted SERVE-HF TrialCanadian Journal of CardiologyVol. 31Issue 9
- PreviewHeart failure (HF) is a complex syndrome that is increasing in prevalence on a worldwide basis and carries a high morbidity and mortality resulting in a huge economic burden. Although HF is initially driven by primary cardiac dysfunction, the syndrome culminates into a multisystem process involving the central nervous system, lungs, kidneys, and skeletal muscles. Targeting the involvement of noncardiac pathways remains an important approach to minimize the progression of HF and to improve clinical outcomes.
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- Reply to Letter From Floras et al.—Central Sleep Apnea: Risk Factor or Pathogenic Process in Patients With Heart FailureCanadian Journal of CardiologyVol. 32Issue 3
- PreviewWe thank Floras et al.1 for their interest in our News and Commentary on the use of adaptive servo-ventilation (ASV) therapy in symptomatic patients with heart failure and reduced ejection fraction.2 As clearly delineated in our News and Commentary, the safety advisory was issued based on the findings of increased mortality in patients receiving ASV in the Adaptive Servo-Ventilation for Central Sleep Apnea in Systolic Heart Failure (SERVE-HF) trial. The actual results of the trial were presented at the 2015 European Society of Cardiology Congress and recently published in the New England Journal of Medicine.
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