Atrial fibrillation (AF) is the most common sustained arrhythmia, and is associated with a
two-fold increase in the risk of premature death. Morbidity and mortality related to stroke,
heart failure, myocardial infarction, and reduced quality of life, are all common in patients
with AF. AF therefore represents a burgeoning public health problem, affecting over 1 million
patients in the UK and resulting in estimated costs of over £450 million per annum. The main
drivers of AF-related costs are hospitalizations (over £270 million for admissions annually)
and outpatient encounters (approximately £50 million for General Practitioner consultations
and £36 million for specialist clinic referrals annually)11. Recurrence of AF remains a
clinical challenge despite pharmacological and interventional rhythm control strategies.
Moreover, currently available therapies have not been consistently shown to reduce AF
recurrence and the risk of major adverse events, or to improve long-term prognosis.
The incidence and prevalence of AF are closely linked to increasing age and excess weight. On
one hand, advanced age is the most important non-modifiable risk factor for AF and the
corollary is that AF is associated with frailty and impaired physical function. Meanwhile,
excess weight is of particular interest as results from four large community-based European
studies clearly demonstrated that elevated body mass index (BMI) is the strongest modifiable
risk factor for incident AF. A large-scale observational cohort study reported a 4% increase
in AF-risk per 1-unit increase in body mass index (BMI) after adjustment for cardiovascular
risk factors and interim myocardial infarction or heart failure. Moreover, a recent Mendelian
randomization study confirmed a causal relationship between increased BMI and incident AF.
The precise mechanisms by which obesity increases the risk of development and maintenance of
AF are incompletely understood; potential contributors include left atrial (LA) enlargement,
left ventricular (LV) hypertrophy, diastolic dysfunction, altered cardiac energetics, and
inflammatory/oxidative signalling from the epicardial adipose tissue.
Very low calorie diets, providing less than 800 kcal/d have been used for many years as
highly effective methods for inducing weight loss, leading to consistent reductions in
visceral fat and overall adiposity. A systematic review showed weight loss at 1 year of 8-14
kg, which was 4.3 kg (95% CI: 1.1 kg, 7.4 kg) greater than the comparator interventions. The
historical limitation of very low calorie diets has historically been long-term
effectiveness, and there has been growing interest in the use of total meal replacement
sachets as part of a wider behavioural programme. This includes individualised one-to-one
counselling to motivate and encourage adherence to the diet, as well as support to establish
a healthy eating plan when individuals reintroduce food. Results from DiRECT (a
cluster-randomised trial assessing a meal replacement programme in patients with type II
diabetes) were published recently in The Lancet: the intervention arm reached an average
weight loss of 10 kg at 1 year with 45% of individuals achieving complete remission of type
II diabetes, which is also a relevant risk factor for AF. Preliminary data suggest that such
a programme proved highly effective in reducing AF symptoms in a relatively young group of AF
patients where the diet resulted in significant weight loss (>10kg) sustained to 15 months.
However, it remains unclear whether the beneficial effects of weight loss translate in (a)
reducing AF recurrences and (b) whether they also extend to the more typical elderly patient
population with AF, as reversing cardiac remodelling may prove more difficult in aged hearts.
Additionally, the balance between beneficial and detrimental effects of weight loss in the
elderly may be dependent on preservation of muscle strength.
The aim of this study is to investigate whether, in older overweight/obese AF patients,
referral to a weight loss programme with meal replacement & behavioral support can reduce
AF-recurrences and improve physical performance compared to usual care.
This is a parallel-group, open-label, randomized controlled study to determine whether
substantial weight reduction through referral to a weight loss programme with meal
replacement & behavioral support in older patients who are overweight/obese with persistent
AF can reduce AF recurrences and symptoms and improve the adverse cardiometabolic profile and
physical performance. The expected duration of such programme is approximately 8 months, with
a total of two study visits (at baseline and at 8 months). AF-related symptoms (primary
endpoint) are assessed at baseline and at approximately 8 months after the commencement of
the intervention using the AFSS symptom score.
Elderly individuals (60-85 years) with elevated BMI (≥27 kg/m2), who are scheduled for a DCCV
with a diagnosis of persistent AF will be recruited. Participants will be randomised (1:1) to
(a) weight loss programme for a total of ~8 months (intervention) or (b) usual care; i.e.,
nurse-based consultation and supporting written material (control). All participants will
undergo a baseline visit (prior to randomisation) and a follow-up visit at ~8 months. Both
study visits will include a physical performance test (PPT), AF symptom assessment using the
AFSS score, anthropometric measurements, quality of life assessment, Patient Health-Resource
Use Questionnaire (PRUQ), MR scan, and blood sample collection. Additionally, prolonged ECG
monitoring, and patient reported outcome measures (PROMs) will also be acquired at the
8-month visit. Finally, at approximately 4 months patients will be asked to complete interim
questionnaires (including PRUQ, PROMs, Quality of Life) by post/telephone.
In the LOSE-AF trial, the intervention is at very low risk of adverse events and no Trial
Steering Committee or Clinical Trial Authorization is required. The study will be coordinated
by the Trial Management Committee (TMC), consisting of at least one core study investigator
(a medically qualified clinician), and the research nurse. The TMC will be responsible for
the day-to-day management of the trial and will meet regularly.