ORLANDO – Adaptive servo ventilation produced a significant and clinically meaningful reduction in atrial fibrillation burden in patients with heart failure and sleep apnea in results from an exploratory, prospective, randomized study with 35 patients.
Adaptive servo ventilation (ASV) “may be an effective antiarrhythmic treatment producing a significant reduction in atrial fibrillation without clear evidence of being proarrhythmogenic,” Jonathan P. Piccini, MD, said at the annual scientific meeting of the Heart Failure Society of America. “Given the potential importance of this finding further studies should validate and quantify the efficacy of ASV for reducing atrial fibrillation in patients with or without heart failure.”
Mitchel L. Zoler/Frontline Medical News
Dr. Jonathan P. Piccini
“A mound of data has shown that treating sleep apnea reduced arrhythmias, but until now it’s all been observational and retrospective,” Dr. Piccini, an electrophysiologist at Duke University in Durham, N.C., said in an interview. The study he reported is “the first time” the arrhythmia effects of a sleep apnea intervention, in this case ASV, was studied in a prospective, randomized way while using implanted devices to measure the antiarrhythmic effect of the treatment.
The new finding means that additional, larger studies are now needed, he said. “If patients have sleep apnea, treating the apnea may be an incredibly important way to prevent AF or reduce its burden”
The CAT-HF (Cardiovascular Improvements With Minute Ventilation-Targeted ASV Therapy in Heart Failure) trial was originally designed to randomize 215 heart failure patients with sleep disordered breathing – and who were hospitalized for heart failure – to optimal medical therapy with or without ASV at any of 15 centers in the United States and Germany. But in August 2015, results from the SERVE-HF (Treatment of Sleep-Disordered Breathing with Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients with Heart Failure) trial, which generally had a similar design to CAT-HF, showed an unexpected danger from ASV in patients with central sleep apnea and heart failure with reduced ejection fraction (N Engl J Med. 2015 Sept 17;373[12]:1095-105). In SERVE-HF, ASV was associated with significant increases in all-cause and cardiovascular mortality. As a result, enrollment into CAT-HF stopped prematurely with just 126 patients entered, and ASV treatment of patients already enrolled came to a halt.
The primary endpoint in the underpowered and shortened CAT-HF study, survival without cardiovascular hospitalization and with improved functional capacity measured on a 6-minute walk test, showed similar outcomes in both the ASV and control arms. But in a prespecified subgroup analysis by baseline ejection fraction, the 24 patients with heart failure with preserved ejection fraction (19% of the CAT-HF enrollment) showed a statistically significant, 62% relative improvement in the primary endpoint linked with ASV treatment compared with similar patients who did not receive ASV, Christopher M. O’Connor, MD, professor of medicine at Duke University, reported in May 2016 at the European Heart Failure meeting in Florence.
Dr. Piccini’s report focused on a prespecified subgroup analysis of CAT-HF designed to examine the impact of ASV on arrhythmias. Assessment of the impact of ASV on atrial fibrillation was possible in 35 of the 126 patients in CAT-HF who had an implanted cardiac device (pacemaker, defibrillator, or cardiac resynchronization device) with an atrial lead, and assessment of ventricular arrhythmias occurred in 46 of the CAT-HF patients with an implanted high-voltage device (a defibrillator or resynchronization device) that allowed monitoring of ventricular arrhythmias.
For the atrial fibrillation analysis, the 35 patients averaged 60 years of age, and about 90% had a reduced ejection fraction. About two-thirds had an apnea-hypopnea index greater than 30.
The results showed that the 19 patients randomized to receive ASV had an average atrial fibrillation burden of 30% at baseline that dropped to 14% after 6 months of treatment. In contrast, the 16 patients in the control arm had a AF burden of 6% at baseline and 8% after 6 months. The between-group difference for change in AF burden was statistically significant, Dr. Piccini reported, with a burden that decreased by a relative 21% with ASV treatment and increased by a relative 31% in the control arm.
Mitchel L. Zoler/Frontline Medical News
Dr. Christopher M. O'Connor
Analysis of the ventricular arrhythmia subgroup showed that ASV had no statistically significant impact for either lowering or raising ventricular tachyarrhythmias or fibrillations.
Trying to reconcile this AF benefit and lack of ventricular arrhythmia harm from ASV in CAT-HF with the excess in cardiovascular deaths seen with ASV in SERVE-HF, Dr. Piccini speculated that some of the SERVE-HF deaths may not have been related to arrhythmia.
“Sudden cardiac death adjudication is profoundly difficult, and does not always equal ventricular arrhythmia,” he said. “We need to consider that some of the adverse events in patients with severe central sleep apnea and low left ventricular ejection fraction [enrolled in SERVE-HF] may have been due to causes other than arrhythmias. The CAT-HF results should motivate investigations of alternative mechanisms of death in SERVE-HF.”
The CAT-HF trial was funded by ResMed, a company that markets adaptive servo ventilation equipment. Dr. Piccini has received research support from ResMed and from Janssen, Gilead, St. Jude, Spectranetics, and he has been a consultant to Janssen, Spectranetics, Medtronic, GSK and BMS-Pfizer. Dr. O’Connor has been a consultant to ResMed and to several other drug and device companies.
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