New insights from the CAT-HF trial show promise for subsets of patients who use adaptive servo-ventilation, but larger studies are needed.

In 2015, when the results of Adaptive Servo-Ventilation for Central Sleep Apnea in Systolic Heart Failure (SERVE-HF) trial were released, it sent ripples through the sleep medicine world.

The clinical trial that involved 1,325 patients with heart failure with reduced ejection fraction (HFrEF) and central sleep apnea showed that the patients who were treated with adaptive servo-ventilation (ASV) had a higher risk of all-cause mortality and cardiovascular mortality than those who were treated with conventional heart failure management.1 These findings led to safety notices issued by the likes of the American Academy of Sleep Medicine (AASM) and have made sleep providers cautious of prescribing ASV therapy to patients with heart failure.

But recent insights from the Cardiovascular Improvements with Minute Ventilation-targeted Adaptive Servo-Ventilation Therapy in Heart-Failure (CAT-HF) trial suggest that ASV therapy could improve cardiovascular outcomes for a subset of patients with moderate-to-severe sleep disordered breathing (because of either obstructive or central sleep apnea). Like SERVE-HF, CAT-HF was funded by ResMed, which markets an ASV device.

The CAT-HF trial looked at the effect ASV therapy has on patients hospitalized for acute decompensated heart failure and who have moderate-to-severe sleep apnea. While the study found that adding ASV to optimized medical therapy didn’t improve 6-month cardiovascular outcomes, it did find that patients in a pre-specified subgroup—those with preserved ejection fraction—saw positive effects of ASV therapy in improving the condition of their sleep-disordered breathing.2 “There are no level of evidence 1A guideline recommended therapies specific for HFpEF [heart failure with preserved ejection fraction] patients, which accounts for half of all people living with chronic heart failure,” says CAT-HF lead investigator and cardiologist Christopher M. O’Connor, MD, CEO of the Inova Heart and Vascular Institute, in a release. “These results from CAT-HF suggest we need to further study the role of whether addressing sleep-disordered breathing can help people who have heart failure with preserved ejection fraction.”

A more recent analysis of data from the CAT-HF trial suggests that ASV treatment may also improve diastolic function—a possibility based on the substantial reductions seen in left atrial volume among patients (with both reduced and preserved ejection fraction) receiving ASV that warrants further study.3

And a CAT-HF prospective substudy of patients with pacemakers/defibrillators published this year provides proof of concept that ASV therapy could reduce atrial fibrillation burden in patients with heart failure and sleep apnea.4

“If we look at the studies overall, we know that the prevalence of sleep apnea both central and obstructive can range from 50% to 75% of patients with heart failure as well as patients with heart arrhythmias,” says Teofilo Lee-Chiong Jr., MD, who was not involved in the studies. Lee-Chiong is chief medical liaison for Philips Respironics, which markets an ASV device. “The challenge is that patients could have both types of apneas, so there is not a one-size-fits-all type of approach that fits all patients.”

Especially when it comes to patients with sleep apnea who also have comorbidities like heart failure or atrial fibrillation, treatments need to adjust according to how their heart conditions are evolving. For instance, if a heart failure patient gets treated for arrhythmia, then his or her treatment of sleep apnea may need adjustment as well.

“It’s expected that you alter your management for patients like this, so ASV is really only part of a combination of therapies available for patients,” says Lee-Chiong, who is also a professor of medicine and pulmonologist at National Jewish Health and author or editor of more than 20 books on sleep medicine and pulmonology.

ASV Over the Years

For physicians like Lee Surkin, MD, who’s board certified in cardiology, nuclear cardiology, and sleep medicine, recommending ASV therapy to patients with heart failure has posed challenges. After SERVE-HF results were released, he recommended that all of his patients with reduced left ejection fraction (less than or equal to 45%) cease ASV treatment. But he’s still had some patients insist on ASV therapy despite being warned of the risks.

How do you make sense of two somewhat conflicting realities that the SERVE-HF trial saw increased mortality risk among patients with reduced ejection fraction, but some patients with reduced ejection fraction have the real-world experience that using the therapy improves their quality of life?

In response to this question, Surkin, who was not involved in the studies, says following practice guidelines is key. “This is where patient education is important so that they understand the implication of these clinical trials—collaborating with patients so they can make a fully informed decision is how I’ve practiced medicine for 22 years,” he says.

While many agree that these findings are encouraging for patients, there’s also agreement that there’s a strong need for a larger clinical study that involves a higher study participant volume. The AASM has not released new practice guidelines in response to the CAT-HF trial.

Right now, there is an ongoing trial known as ADVENT-HF (sponsored by the Toronto Rehabilitation Institute with Canadian Institutes of Health Research and Philips Respironics as collaborators) that looks at the effect ASV has on survival and hospital admissions in heart failure, which has the potential to provide additional insight into the cause of mortality and the impact of improved ASV compliance.

It’s important to note that the populations of the trials aren’t entirely analogous. Adam Benjafield, ResMed VP of medical affairs, says, “The positive finding from CAT-HF was in HFpEF patients with sleep-disordered breathing (OSA and/or CSA), not in the SERVE-HF population of HFrEF with CSA; ADVENT-HF is HFrEF with sleep-disordered breathing (OSA and/or CSA), so the positive finding from CAT-HF is not directly relevant to ADVENT-HF.”

Surkin, who founded the American Academy of Cardiovascular Sleep Medicine in an effort to increase collaboration among sleep medicine and cardiology providers, says, “There’s clearly plenty of work to be done to refine and define practice guidelines in this arena and as providers, we need to migrate to a more interdisciplinary approach.”

What’s more, according to Surkin and Lee-Chiong, more conversations among providers from different disciplines and between patients and providers are needed.

“We should look at ASV as part of the solution for the patient and not just a single treatment,” says Lee-Chiong. “In the past, physicians have taken a prescriptive approach to care but now the emphasis should be on taking less of a fragmented approach in treating patients as a whole and engaging in more of a continuous dialogue with patients.”

Yoona Ha is a freelance writer and healthcare public relations professional.


1. Cowie MR, Woehrle H, Wegscheider K, et al. Adaptive servo-ventilation for central sleep apnea in systolic heart failure. N Engl J Med. 2015;373:1095-1105.

2. O’Connor CM, Whellan DJ, Fiuzat M, et al. Cardiovascular Outcomes with Minute Ventilation-Targeted Adaptive Servo-Ventilation Therapy in Heart Failure: The CAT-HF Trial. J Am Coll Cardiol. 2017 Mar 28;69(12):1577-87.

3. Daubert MA, Whellan DJ, Woehrle H, et al. Treatment of sleep-disordered breathing in heart failure impacts cardiac remodeling: Insights from the CAT-HF Trial. Am Heart J. 2018 Jul;201:40-8.

4. Piccini JP, Pokorney SD, Anstrom KJ, et al. Adaptive servo-ventilation reduces atrial fibrillation burden in patients with heart failure and sleep apnea. Heart Rhythm. 2019 Jan;16(1):91-7.

UPDATED 4/17/19 to add quote from Adam Benjafield and sponsors/collaborators for ADVENT-HF trial.