Physiotherapist-led Exercise Within Cardiac Rehabilitation and Paroxysmal Atrial Fibrillation and COVID-19.

Introduction Paroxysmal atrial fibrillation (AF) induce, in the affected patient an increased
risk of stroke and heart failure. The corner stone in the medical treatment for AF is
anticoagulants and heartrate regulators which affect the physical fitness. Other
interventions available for rhythm regulation such as antiarrhythmic drugs, cardioversion and
catheter ablation are alternatives aimed to be relief the symptoms of AF and increase the
health-related quality of life (HR-QoL). Despite this advanced pharmacologic- and
electrotherapy studies evaluating Patient Related Outcomes measures (PROMs) have shown that
the symptoms persist and the HR-QoL is still reduced after treatment. Furthermore, Gleason et
al, have recently shown that women have a comparatively higher frequency of symptoms, anxiety
and depression despite type of intervention. The majority > 90 %, of the patients with
paroxysmal AF have symptoms such as palpitations, chest pain, reduced physical fitness and
breathlessness. The unpredictability regarding the source of an AF attack, duration and
frequencies causes the patient suffering, high healthcare utilization and increased sick
leave, this result in high expenditures for AF related causes both for the patient and
society. To avoid physical activity and exercise due to fear of an AF attack is not unusual,
which may further lead to a reduced physical fitness i.e maximal oxygen capacity (VO2max) and
an increased risk of stroke and mortality. This may lead to an evil circle with additional
reduced physical fitness, possibly an increase in symptoms and a more reduced HR-QoL. The
underlying causes of reduced physical fitness and breathlessness associated with AF is
probably multifactorial. One reason could be skeletal muscle abnormities as in heart failure,
which often coexists with AF. An increased mortality in the novel Coronavirus (COVID-19)
caused by the SARS-CoV-2 is seen in individuals with older age, cardiovascular disease and in
men, and the most usual complication is arrythmia such as AF. COVID-19 is a disease that
affect the persons lungs and it is not uncommon with pulmonary complications. This can lead
to an increased demand for exercise-based rehabilitation in patients with AF and reduced
inspiratory muscle strength. One study has shown that a reduced respiratory muscle function
can positively be affected with inspiratory muscle training in patients with permanent AF.
Furthermore, a Cochrane report have shown that exercise can improve physical fitness in
patients with AF, however, no effect was seen in HR-QoL. However, patients with paroxysmal
AF, were underrepresented and additional studies concerning patients with paroxysmal AF are
requested. Whether physiotherapist-led exercise-based cardiac rehabilitation (PT-X) and
inspiratory muscle training (IMT) can improve physical fitness and positively affect symptoms
and consequently improve HR-QoL is to our knowledge not studied.

Aim Primary to investigate, in a multicentre randomised controlled trial, if PT-X in
combination with IMT can impact HR-QoL in patients with paroxysmal AF. Secondary to
investigate the effect of PT-X in combination with IMT regarding symptoms, physical fitness,
physical activity and the number of atrial fibrillation attacks and health care costs
compared to the control group, asked to live their usual life, during the study period.
Further to investigate the prevalence of antibodies for SARS-CoV-2, and the patient's own
experience of how COVID-19 has affected their incidence and symptoms of paroxysmal AF.

Question formulations:

Primary question How will participation in PT-X and IMT impact the short form SF-36 general
health score compared to the control group that is allowed to continue with their usual life?
Secondary questions How will participation in PT-X and IMT impact the exercise capacity
compared to the control group that is allowed to continue with their usual life? How will
participation in PT-X and IMT affect symptoms of AF and fatigue compared to the control group
that is allowed to continue with their usual life? How will participation in PT-X and IMT
affect the muscle function compared to the control group that is allowed to continue with
their usual life? How will participation in PT-X and IMT affect the frequency, duration and
number of AF attacks compared to the control group that is allowed to continue with their
usual life? How is the incidence of depression among the participants in the study, and is it
possible to impact the prevalence of AF with participation in PT-X and IMT compared to the
control group that is allowed to continue with their usual life? How has the COVID-19
affected the patient's own experience of number of attacks, symptoms and duration of AF? How
is the prevalence of antibodies for SARs-CoV-2 among the participants in the present study?
Method Study design A multi-centre randomised controlled trial Patients A total of 180
patients with paroxysmal AF, age 40 - 85 years, visiting the cardiology clinic at SV Hospital
group Alingsås Hospital, Sahlgrenska University Hospital and primary care will be asked to
participate in the study. Advertising in the daily press will be made for participants with
paroxysmal AF. The patients will be informed both verbal and in written information, and a
written informed consent will be obtained.

Statistics and power calculation The patients will be randomised stratified after sex, age
and exercise capacity measured by the symptom-limited ergometer cycle test. Ratio and
interval data will be presented as mean (± 1 SD), ordinal data will be presented as median
(range) and nominal data in absolute and relative numbers. Depending on if the data are
normal distributed or not the Student T-Test or the Mann-Whitney U- test will be used for
evaluation of differences between the groups. Chi2 test will be used for evaluation of
differences between the nominal data.

The sample size was calculated using a power (β) of 80% and a significance level of (α) 5%.
Based on the assumption of a mean (SD) significant (p=0.05) difference in the PT-X group
compared to the control group regarding improvement of SF-36 General Health score of 7.5 ± 15
points a total of 76 patients are needed in each group. Based on the assumption of a
calculated withdraw of approximately 20% a total of 180 participants are needed to be
included in this study.