Time to implement fitness and reduction of fatness in atrial fibrillation therapy

This editorial refers to ‘Self-reported physical activity and major adverse events in patients with atrial fibrillation: a report from the EURObservational Research Programme Pilot Survey on Atrial Fibrillation (EORP-AF) General Registry’ by M. Proietti et al., on pages 535–543. Atrial fibrillation (AF) is not a benign condition and contributes importantly to cardiovascular morbidity and mortality. Until recently, only non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonist OACs have been associated with reduction of mortality,1 but not rhythm control therapy. Regular not-vigorous physical activity and respiratory cardiofitness are protective against cardiovascular diseases and all-cause mortality.2,3 Physical activity, especially vigorous exertion and endurance sports, however, has been associated with an increased risk of AF.4 Yet, there is increasing evidence that moderate physical activity and cardiorespiratory fitness are associated with a reduced risk of AF.5 For example, in obese patients (body mass index ≥27 kg/m2), baseline cardiorespiratory fitness was associated with a higher freedom of AF. Furthermore, an improvement in cardiorespiratory fitness (≥2 metabolic equivalents) during follow-up contributed to a further AF burden reduction in association with weight loss, an improvement of glycaemic and lipid control, a reduction in blood pressure, a decrease of atrial and ventricular sizes, and increase in diastolic function and a reduction of systemic inflammation.5 However, data on the effects of physical activity on outcome in patients with AF are lacking. In the current issue of EP-Europace, Proietti et al.6 report on the relationship between physical activity and major cardiovascular outcomes in AF patients prospectively enrolled in the EURObservational Research Programme on AF (EORP-AF) Pilot Survey conducted in nine European countries. Their aim was to assess, for the first time, the relationship between physical activity and cardiovascular outcomes and all-cause mortality in patients with AF, and particularly to determine how absence of physical activity was associated with worse outcomes. Secondly, they intended to unravel the influence of physical activity on AF progression, defined as paroxysmal AF deteriorating into persistent or permanent AF. Patients eligible for the study were consecutive patients admitted to the hospital or referred to office-based cardiology centres who had AF recorded as primary or secondary disease. Follow-up was 1 year. During the enrolment interview, patients self-reported their level of physical activity preceding the last 2 years: (i) none: no exercise or <3 h/week for <2 years; (ii) occasional: <3 h/ week ≥2 years; (iii) regular if ≥3 h/ week for ≥2 years; and (iv) intense if > 7 h/week for ≥2 years. Data on physical activity were available in 2442 (79%) of the 3119 patients: no physical activity was performed by 39%, occasional by 35%, regular by 22%, and intense physical activity by a minority, 5%. The mean age was 74, 69, 65, and 64 years in the no exercise, occasional, regular, and intense exercise groups, respectively (P < 0.0001). Patients who practiced increasing levels of physical activity were more often male and had fewer co-morbidities and lower CHA2DS2-VASc scores. Overweight or obesity was present in 69, 73, 72, and 65% in the no exercise, occasional, regular, and intense exercise groups, respectively. The most important finding of this study was that during 1 year of follow-up patients who self-reported (almost) no physical activity had a higher all-cause mortality compared with all physically active patients (12.2 vs. 3.9, 1.3, and 2.6% in the no exercise, occasional, regular, and intense exercise groups, respectively, P < 00001), which was true for women and men. Further, cardiovascular mortality (5.8 vs. 1.4, 0.4, and 0.9% in the no exercise, occasional, regular, and intense exercise groups, respectively, P < 0.0001) and the composite outcome of all-cause death and any thromboembolic complication (16.6 vs. 7.5, 5.5, and 5.6% in the no exercise, occasional, regular, and intense exercise groups, respectively, P < 0.0001) were higher in the physically inactive group. The progression of AF was assessed in 603 (25%) patients with paroxysmal AF at baseline. At 1-year follow-up, 88 (15%) showed AF progression to more persistent or permanent forms of AF. Patients with AF progression were older and more frequently underweight. Levels of physical activity were not significantly associated with AF progression although the percentage of patients showing AF progression progressively decreased with increasing levels of physical activity (18% in the no exercise group vs. 7% in the intense physical activity group). The authors deserve congratulations for their contribution to the awareness of the favourable effects of moderate physical activity in AF. This is a first report showing the impact of fitness on adverse outcomes in patients with AF. Prior data elucidated beneficial effects of fitness and reduced obesity on rhythm control outcome in obese patients with AF. Intensive weight reduction on top of the management of other cardiovascular risk factors (10–15 kg weight loss achieved in obese patients with a BMI ≥27 kg/m2) was accompanied by a reduction in AF burden and symptoms compared with a routine treatment strategy. Cardiorespiratory fitness at baseline and enhanced cardiorespiratory fitness during follow-up further decreased AF burden, in association with weight loss, a reduction in blood pressure, lipids, inflammation, and an improvement of glycaemic control.5 These data highlight the role of fitness in combination with loss of weight in obese patients for rhythm control outcome and risk factors for cardiovascular morbidity. The present study extends these findings to at least a strong suggestion that fitness is associated with an improved prognosis in patients with AF.6 Undeniably, the study includes important limitations, which has also been acknowledged by the authors. The follow-up was rather short, which implies a low number of events. Physical activity was self-reported. No objective assessment of exercise capacity, i.e. metabolic equivalent, was done. Indeed, the distribution of relevant confounders such as age, obesity, diabetes, and hypertension seem skewed in favour of patients who are more physically active. This may be a vicious circle in which co-morbidities limit physical activities and increase risk of AF. This may cause physical activity to appear more protective than its true effect. Finally, for the assessment of AF progression, only limited electrocardiographic recordings were available. The strength of the present data, however, is that they come from a real-world AF population of consecutive in- and outpatients enrolled in nine European countries. Why are these data so important? Despite major advances, especially in non-pharmacological rhythm control therapy, AF is difficult to treat. Success of rhythm control outcome with the use of atrial ablation is definitely increasing, especially in paroxysmal selfterminating AF, but still far from optimal. Further, morbidity and mortality remain substantial. AF is associated with a two-fold increased risk in all-cause mortality in women and 1.5-fold increase in men. A recent retrospective cohort study of Medicare beneficiaries 65 years and older with AF showed that mortality was 20% after 1 year increasing to 49% after 5 years.7 Heart failure hospitalizations occurred in 6 and 14%, respectively. Despite many developments, only (N)OACs have been associated with reduction of mortality.1 Fitness and reduction of obesity are now recognized to influence outcomes in healthy adults and patients with cardiovascular diseases by a reduction of cardiovascular disease risk factors including hypertension, metabolic syndrome, and hypercholesterolaemia and, most importantly, a reduction in all-cause and cardiovascular mortality.2,8 Possible mechanisms include weight loss, improvement of lipid profile, reduction in blood pressure, improvement of endothelial function, reduced systemic inflammation, and improvement of psychological well-being.3 The present study adds to these data that also in real-life AF patients fitness is associated with improved outcome. It brings our attention to the relevance of lifestyle changes instead only concentrating on improving rhythm control outcome. Certainly, more research is warranted to demonstrate a causal relationship between physical activity and outcome and to prove the feasibility of active participation of AF patients to change their lifestyle and to ensure adherence to therapy. In the RACE 3 (Routine versus Aggressive upstream rhythm Control for prevention of Early atrial fibrillation in heart failure) trial, we investigate whether the combination of upstream therapies and cardiac rehabilitation including interventions to promote physical activity, weight reduction, and a healthy diet may reduce progression of AF in persistent AF patients as well as cardiovascular morbidity and mortality compared with routine therapy.9 Time has come to be concerned about the lifestyle in every AF patient and to implement lifestyle changes in our comprehensive management approach in AF patients.10 We acknowledge the support from the Dutch Heart Foundation [NHS B 2008 035; Routine versus Aggressive upstream rhythm Control for prevention of Early atrial fibrillation in heart failure (RACE 3); I.C.V.G., A.H.H., J.B., and M.R.] and from the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation [CVON 2014-9; Reappraisal of Atrial Fibrillation: interaction between hyperCoagulability, Electric remodeling, and Vascular destabilisation in the progression of AF (RACE V); I.C.V.G. and M.R.]. Conflict of interest: none declared.