The effectivity of lifestyle interventions and prevention in patients with atrial fibrillation referred for ablation; a randomised-controlled trial

Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting around
2% of the world population and its prevalence is expected to rise due to an
aging population. This rise is accompanied with increasing rates of stroke,
hospitalisation for heart failure and death. The burden of AF is mainly
determined by hospitalisations, heart failure and thrombo-embolic events.
Treatment of symptomatic AF consists of antiarrhythmic medication and catheter
ablation. AF recurrence rate after 1 year is up to 60% with catheter ablation,
with most recurrences in the first 6 months. Poor long-term outcomes may be due
to inability to attenuate the progressive substrate for AF. Several modifiable
risk factors have been linked as promoters for AF. Among those risk factors are
obesity, hypertension, obstructive sleep apnea (OSA) and smoking. Treatment of
these risk factors results in better AF outcomes. For example, long-term weight
loss is associated with a 6-fold greater freedom from AF during 5 year
follow-up. Bariatric surgery prior to AF ablation resulted into more freedom
from AF. The RACE3-trial showed that AF patients with heart failure were more
likely to remain in sinus rhythm if they were treated for their heart failure
and hypertension. The ARREST-AF study also evaluated the effect of multiple
risk factor management on ablation outcomes and showed improved AF burden and
improvement of symptoms. The study might have been biased because of its
observational design.
A nurse-led AF clinic has previously shown improvement in guideline adherence
and patient education. Integrated care consists of community support and a
multidisciplinary team, including an AF specialist nurse, a dietician, a sleep
physician and an electrophysiologist. Integrated care approach is associated
with a reduction in all-cause mortality and cardiovascular hospitalisation in a
population with atrial fibrillation. Furthermore, integrated care leads to
lower health care costs, because future health consumption is lower.
Less is known about impact on patient value and quality of life (QoL). The
CAPCOST trial showed that AF recurrences of more than 30 seconds up to 2 hours
a month do not affect quality of life outcomes. Measuring total freedom from AF
is not a good predictor for QoL in AF patients. At this point, there is not
sufficient knowledge available about whether patients benefit from a
specialized care outpatient clinic to treat the modifiable risk factors,
including screening for OSA and lifestyle. We will be the first to test the
effectiveness of a nurse-led outpatient clinic applying innovative technologies
for personalized risk factor management and life style optimization in a
prospective randomized controlled trial.
To our knowledge, this is the first large-scale study of its kind with patients
that are referred for AF ablation. We hypothesize that an improved
individualized and technology-supported care can improve patient value in
atrial fibrillation.

This study aims to validate an integrated care model that is standardized and
can easily be carried out in any other hospital.

Primary objective
The primary objective is to determine the effect of a nurse-led,
technology-supported, personalized care pathway on hospital admissions for
cardioversion and re-ablation when compared with usual clinical care in
patients with AF that are referred for ablation.

Secondary Objectives:
There are multiple secondary objectives.
- To determine cost-effectiveness and patient value as defined by Porter
- To evaluate ablation success rate in terms of the use of antiarrhythmics
after three months
- To determine the effect on cancelation or deferral of the index ablation
- To determine general Quality of Life, using the EuroQol-5D questionnaire and
to determine AF-related Quality of Life using the AFEQT questionnaire
- To determine the burden of Treatment using the Treatment Burden Questionnaire
- To evaluate the effect of treatment on the respective modifiable risk
factors, using vital functions, weight and lab results.
- To test the role of OSA detecting technology (WatchPAT) in the AF population
that is referred for atrial ablation, compared to other screening tools
- To evaluate patient experience and its main determinants in the new
outpatient clinic
- To evaluate staff experience and its main determinants in the new outpatient
clinic

This is a prospective, randomized, open label controlled trial. The study is
performed in the Catharina hospital Eindhoven, a tertiary care hospital with
regards to electrophysiology and ablation procedures. Patients with paroxysmal
or persistent symptomatic atrial fibrillation that are referred for their first
catheter ablation (also called the index ablation) are included in the
prospective trial. Patients are randomized to standard clinical care or a
highly specialized outpatient clinic for atrial fibrillation. This includes OSA
screening with a specialized device (WatchPAT), screening and treatment of
other modifiable risk factors and detailed questionnaires. The WatchPAT device
has been validated for screening and detecting OSA in patients with AF (14). A
nurse practitioner will also focus on lifestyle aspects with self-reporting
technologies. Patients assigned to the usual-care group will have the ablation
at standard time, without experiencing further delay. Patients assigned to the
extensive care group will first receive treatment for their relevant risk
factors and then undergo the ablation. The ablation will not be delayed for
more than 6 months. We aim at treating the risk factors as soon as possible.
If there are too many risk factors to be treated in a for the patient
reasonable way, the physician will decide which risk factors will be treated.
After the index ablation there is a follow-up time of 12 months. If patients
have successful treatment at the outpatient clinic, this may lead to
improvement of their AF symptoms and the possibility to cancel the planned
ablation will be discussed with their treating cardiologist. Patients will
still have a follow-up of 12 months after finishing treatment at the outpatient
clinic.
We aim for a clear methodology so this study can be replicated and results can
easily be applied in daily practice.

The investigational treatment consists of multiple outpatient clinic visits
which are conducted by a specialized nurse practitioner. The modifiable risk
factors will be assessed during the intake visit, and relevant interventions
are planned. In order to assess all of the risk factors, the patients are
subjected to blood sampling, the measuring of vital functions and the WatchPAT,
a home sleep apnea testing device, which is worn for one night. Lifestyle
changes and medications will respectively be prescribed for weight management,
blood pressure control, lipid management and glycaemic control. If applicable,
patients will receive treatment for their OSA. The specific risk factor
treatment plans are specified more clearly below in this section.
Patients are offered education and training concerning atrial fibrillation by
face-to-face counselling. In order to achieve relevant behaviour changes
related to the AF risk factors, behavioural determinants such as knowledge,
self-efficacy and attitude will be addressed. Behavioural models such as the
Integrated Behavioral Model (IBM) are used to understand the relevant
determinants and intervention mapping will be used to systematically develop an
evidence-based intervention to initiate and maintain changes in alcohol
consumption, smoking, dietary and physical activity behaviour.
Patients are instructed to use the VitalHealth Engage platform. This is a care
platform for communication and care coordination. The patient can use the
platform at home to report AF complaints, send home measurements (e.g. blood
pressure) and can complete questionnaires. Furthermore, the platform can be
regarded as an extension to the outpatient clinic visits. It supports the nurse
practitioner in patient education and lifestyle changes, by providing the
patient personalized content.
The time patients will spend undergoing the investigational treatment depends
on which of the risk factors will be treated. We aim at finishing all
treatments within 6 months after inclusion. If the patient has completed all
relevant therapies or if 6 months have passed, the patient will undergo the
ablation. If there are too many risk factors to treat within 6 months in a for
the patient reasonable way, one or multiple risk factors might be ignored at
the physicians discretion. After patients have had their index ablation, they
will not receive any active further treatment of their risk factors. Patients
are encouraged to continue their lifestyle treatment with support of the
general practitioner. Patients in the control group will not visit the
nurse-led outpatient clinic. They will immediately be planned for ablation.
They will use the Engage app to answer quality of life questionnaires. The
treating cardiologist is allowed to do interventions in the comparator group as
he would normally do.
The several risk factor treatment plans and targets are specified in this
section.

Blood pressure control
Blood pressure is measured during the first outpatient clinic by the nurse
practitioner. Target blood pressure is systolic <140 mmHg and diastolic <90
mmHg. For patients with diabetes mellitus we target a blood pressure of 130/90
mmHg. Treatment is according the 2018 ESC Guidelines for the management of
arterial hypertension. All hypertensive patients were advised a dietary salt
restriction (<100 mmol/day; <5 gram/day).
Blood pressure monitoring at home is considered for follow-up and evaluating
therapy success. During the last outpatient clinic visit before ablation a
final blood pressure measurement will take place.

Lipid management
At the intake blood lipid analysis is done. The sample can be taken in a
non-fasting state, since non-fasting samples have the same prognostic value as
fasting samples. Patients are treated conform ESC 2019 guidelines on
dyslipidaemias management. This may involve lifestyle changes and consultation
of a dietitian. Eventually, this also leads to treatment with an HMG-CoA
reductase inhibitor or a cholesterol absorption inhibitor. Fibrates are used
for isolated hypertriglyceridemia. Evaluation of therapy takes place at 3
months with a new blood lipid analysis.

Glycaemic control
In patients with known diabetes, target HbA1c was <53 mmol/mol. Better
treatment of hyperglycaemia was advised to the physician responsible for the
treatment of diabetes, for example, the general practitioner or the
endocrinologist. This may also include the consultation of a dietitian.
Diabetes mellitus de novo was suspected in patients with HbA1c >48 mmol/mol and
fasting plasma glucose >7.0 mmol/L. They will be referred to their general
practitioner for further treatment. During the last outpatient clinic visit
before ablation new HbA1c check will take place/

Alcohol
Alcohol reduction is promoted on the outpatient clinic. Men who drink alcohol
should be advised to limit their consumption to 14 units per week and women to
8 units per week (1 unit is equal to 125 mL of wine or 250 mL of beer).
Alcohol-free days during the week and avoidance of binge drinking are also
advised. More strict alcohol reduction is promoted in patients that also follow
the hypertension and weight management program.

Smoking
Smokers were offered support with smoking cessation. They were offered a
training by a certified nurse and a smoking cessation programme that lasts
approximately 6 weeks.

Obstructive Sleep Apnea
Obstructive sleep apnea is diagnosed with the WatchPAT device. The WatchPAT
device has recently been approved for screening and detecting OSA in patients
with AF. All patients in the specialized outpatient clinic will wear the
WatchPAT for one night. This results in the probable diagnosis and severity of
obstructive sleep apnea. A sleep physican will be consulted for further testing
and treatment of OSA. Therapy is offered when AHI was >5/hour.

Weight management
Patients were defined as overweight when they had a body mass index (BMI) above
27 kg/m2. Weight reduction was promoted by offering support counselling and a
meal plan with a dietician. This consists of a low-calorie meals with a low
glycaemic index. Support focused on behaviour modification. At first, we target
a >10% weight reduction. If patients were still overweight after reaching this
goal, further weight loss is promoted. We aim at having a healthy diet low in
saturated fat with focus on wholegrain products, vegetables, fruit and fish.
Lifestyle advice constituted dietary salt restriction 5 gram/day.

Physical (in)activity
Patient are offered to participate in a physical activity programme. Overweight
patients will be recommended to improve physical activity, with a target of
3.5-7 hours of merely vigorous physical activity per week or 30-60 min most
days. Regular aerobic exercise (e.g. at least 30 min of moderate dynamic
exercise on 5-7 days per week) is recommended. Patients that endure complaints
during exercise are also offered support with physical activity at a
specialized cardiac rehabilitation centre. This includes training under
supervision of a physiotherapist twice a week during an hour.

To some extent there might be a burden for patients in both the interventional
and control group.
Patients from the interventional group will have to visit the hospital at least
4 times in 18 months of participation. The first visit will last 45 minutes;
follow-up visits will last 10 minutes. Patients will have a physical
examination, the will have an ECG and they will have blood sampling. At 4
different moments the patients will have to fill out questionnaires. Patients
will undergo a sleep examination at home during one night. This involves
wearing a sensor at night. The burden for patients is estimated to be at least
17 hours. More hospital visits and consultations with a dietician,
physiotherapist or somnologist will come on top of this, depending on relevant
risk factors.
Patients from the control group will have a burden of 3 hours. They will
undergo blood sampling three times in 18 months. The will also have to answer
questionnaires in the Engage app three times in 18 months.
The risk for participants in the interventional group is that their ablation
will be delayed for a maximum of 6 months, depending on their risk treatment
strategy.
Participants in de control group will not experience any delay of intervention.