Weight loss may not improve symptoms of persistent atrial fibrillation in older, overweight patients once structural cardiac changes are established, new research suggests.
The study, led by researchers at Oxford University and published in JAMA [link here], showed that a structured low calorie and behavioural support programme was linked with significant weight loss at eight months, with no safety concerns.
However, there was no statistical difference in AF symptoms, burden, cardiac remodelling, or the need for further rhythm control between the intervention and control groups at follow-up.
Nor were there significant differences in blood pressure or in levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, CRP, interleukin 6 or N-terminal pro-brain natriuretic peptide between the groups.
The results underscore the challenges of treating an elderly population with a disease of longer duration, and contrast with previous studies involving younger populations with less advanced illness, the researchers noted.
“In addition to being older, almost half the participants in the current study had long-standing persistent AF, suggesting more advanced atrial remodelling than those in previous trials,” they wrote.
“These factors are all associated with treatment resistance and more complex arrhythmia mechanisms and may indicate reduced capacity of the atrial myocardium for reverse structural or electrical remodelling.”
The unblinded, randomised LOSE-AF trial was conducted at two UK hospitals and involved 119 patients, aged 60 to 85 (mean age 68) with body mass index of 27 or greater, undergoing direct current cardioversion (DCCV) for AF.
Participants were randomised to an eight-month, low-calorie diet and behavioural support programme (intervention, n=59) or to usual care (control, n=59).
Those in the intervention group saw weight loss from baseline to eight months of 9.7%, compared with 3.1% in the control group (p<0.001).
However, there were no significant differences between the groups in the Atrial Fibrillation Severity Scale (AFSS) symptom severity scores (baseline-adjusted mean at 8 months, 7.9 in the intervention group vs 8.9 in the control group; p=0.43) or in AFSS symptom burden scores.
Notably, physical performance test (PPT) scores were also unaffected by weight loss, with eight-month scores identical between the intervention and control groups (32.6 vs 32.6; p=0.99).
At the follow-up CMR, 43% of total participants were experiencing AF (44% in the intervention group vs 42% in the control group).
Those in the intervention group still had a significantly lower body weight than those in the control group at the long-term follow-up of 3.5 years (95.6 kg vs 100.5 kg; p<0.001; estimated difference, 4.9 kg). However, no significant differences were observed in long-term AFSS symptom severity, symptom burden.
Overall, the results showed that “moderate dietary weight loss was not an effective treatment strategy in this trial in older patients with persistent AF,” the authors concluded.
However, they also noted that the weight loss achieved in the trial was moderate, in keeping with a dietary and lifestyle intervention rather than pharmacological weight loss or bariatric surgery, making it insufficient to produce a significant improvement in blood pressure, lipid levels, or CRP levels in this cohort.
Key limitations
In an accompanying editorial [link here], Dr Gregory Marcus of UCSF Health in San Francisco, USA, stressed nearly half of the participants in each group had long-standing persistent AF, ie, continuous AF for at least 12 months.
“This particular form of atrial fibrillation is notoriously recalcitrant,” he said. “Indeed, a prior observational study concluded that long-standing persistent atrial fibrillation may specifically be resistant to the benefits of weight loss.”
Beyond that, intervention participants did not reach the guideline-recommended goal of at least 10% weight loss, Dr Marcus pointed out.
“This issue highlights a particularly relevant point, which is precisely the difficulty in actually achieving and maintaining prescribed amounts of weight loss,” he said.
“If the guideline-directed goal of 10% or more weight loss could not be achieved in this well-resourced clinical trial that included ongoing support toward that aim, how are busy clinicians expected to do any better?”
Dr Marcus also noted that participants did not appear to be given any help with other lifestyle modifications, such as reducing alcohol intake or being screened for sleep apnoea, while it was unclear whether prescriptions of antiarrhythmic drugs differed between the two groups during the study.
“One reasonable conclusion to take from this study may be that long-standing persistent atrial fibrillation is unlikely to be amenable to weight loss,” he said. “This fits well with growing evidence that early intervention for atrial fibrillation tends to be especially effective.”
“Rather than taking findings from the current study as supporting inaction with respect to weight loss, these current data, alongside prior evidence, may spur on a sense of urgency to help patients with healthy lifestyle choices as soon as an atrial fibrillation diagnosis is made,” he concluded.