Trimming the fat, soothing the heart: Mediterranean diet as a potential game-changer for prevention of atrial fibrillation?

This editorial refers to “Mediterranean diet and epicardial adipose tissue in patients with atrial fibrillation treated with ablation: a substudy of the ‘PREDIMAR’ trial”, by M.T. Barrio-Lopez et al., https://doi.org/10.1093/eurjpc/zwad355. The estimated lifetime prevalence of atrial fibrillation (AF) is ∼25% and is expected to increase further globally.1 The lifestyle choices can have an impact on the development and recurrence of AF. For instance, obesity in particular is a modifiable risk factor contributing to the pathophysiology of AF, with recent focus shifting towards the role of epicardial adipose tissue (EAT).2,3 Rather than overall fat distribution, EAT has especially garnered growing concern for its specific association with AF. A recent meta-analysis of 22 studies showed that EAT is not only associated with the development and recurrence of AF but also related to its severity.4 Given its critical role in the development and advancement of cardiovascular disease, EAT may be a promising therapeutic target for AF.5 Current European Society of Cardiology (ESC) guidelines recommend the adoption of Mediterranean Diet (MedDiet) to prevent cardiovascular disease (Class IA recommendation).6 Although literature supporting the impact of MedDiet on cardiovascular health exists, there remains a lack of concrete evidence to specifically recommend MedDiet for preventing AF owing to potential reductions in EAT. In this context, Barrio-Lopez et al.7 should be congratulated on their excellent analysis in the substudy of the PREDIMAR trial, published in this issue of the journal. This study examines the effect of MedDiet adherence on EAT in patients with AF treated with ablation, contributing significantly to the current scientific dialogue regarding the complex interplay among MedDiet, AF outcomes following ablation, and EAT. Seven hundred and twenty patients were recruited from four institutions in Spain. Of these, 199 patients were included in this substudy based on a pre-ablation computed tomography (CT) scan protocol. Non-contrast cardiac CT scans were taken using a prospective electrocardiogram triggering mode to quantify EAT. To improve the reliability and accuracy of the EAT measurements, trained technicians and physician experts in cardiac CT were involved, and inter-observer variability was evaluated yielding a good correlation. The study used validated questionnaires that certified dietitians administered during a subsequent 4-year period. This approach enhances the methodological robustness of the study. However, some limitations should be considered while interpreting results, such as the limited sample size, and non-random selection of patients. This substudy of the PREDIMAR trial reveals several key findings that render MedDiet as a promising preventive measure for AF through targeted reductions in EAT. First, adherence to a MedDiet (≥7 points in the MEDAS questionnaire) was associated with a statistically significant lower risk of having EAT ≥ 135 g. Second, EAT ≥ 135 g was significantly associated with persistent AF. Lastly, while adherence to MedDiet may help lower the chances of AF recurrence, the results of this substudy failed to reach statistical significance. Although a recent meta-analysis had revealed that patients with AF undergoing ablation are likely to have greater EAT volumes, results from this substudy suggest that patients with AF recurrence following ablation may not always have higher EAT volumes.4 Nonetheless, the non-significant trend towards reduction of AF recurrences with MedDiet (hazard ratio: 0.78, 95% confidence interval, 0.47–1.31) holds important clinical implications. Since EAT >135 g was associated with the presence of persistent AF, targeting reductions in EAT using MedDiet can still hold clinical significance for managing AF. Further investigation is needed to better understand how MedDiet impacts AF outcomes, considering the various contexts and mechanisms involved. While the authors noted that the protective effects of MedDiet were greater in the first 12 months and were not sustained over a longer follow-up duration, this finding may be the result of the low statistical power of this substudy and needs to be confirmed over longer follow-up times and in different settings. Expanding on the framework of the PREDIMAR trial, this substudy establishes a foundation for subsequent inquiries into the intricate relationships among dietary patterns, EAT, and cardiovascular well-being. It underscores the need for further research to corroborate and develop these preliminary findings. Further research is needed to investigate interventions that focus on reducing EAT and how they affect AF. This substudy suggests that EAT > 135 g is associated with AF and MedDiet may be a potential dietary intervention to prevent AF and improve AF outcomes by lowering EAT. However, it is important to recognize that there are other treatment options which can also potentially lower EAT. Notable among these are the SGLT-2 inhibitors, GLP-1 receptor agonists, and newer obesity drugs such as tirzepatide, which have demonstrated potential in decreasing adipose tissue. Studies have demonstrated that tirzepatide effectively decreases adipose tissue throughout the body, including fat in the liver and abdomen.8 Furthermore, studies on SGLT-2 inhibitors and GLP-1 receptor agonists indicate potential impacts on fat tissue and overall metabolic well-being.9 A recent review showed that EAT expresses some specific genes and proteins which can potentially be the target of GLP-1 receptor agonists.10 While detailed data on EAT and AF outcomes are lacking, these studies suggest a broader impact of these drugs on adipose tissue. Future research should aim to compare the effectiveness of MedDiet with these pharmacological agents, not only in terms of their impact on EAT but also in evaluating their ability to prevent AF and its recurrence. In summary, Barrio-Lopez et al. should be congratulated for this substudy of the PREDIMAR trial, which shows that EAT > 135 g is associated with AF and adherence to MedDiet can lead to reductions in EAT which can help prevent AF. The broader scope of lifestyle factors in the PREDIMAR experiment raises further concerns. How do these lifestyle factors jointly impact the effectiveness of AF ablation? Do nutrition, physical activity, and other behaviours synergistically reduce AF recurrences? Can dietary interventions targeting EAT be the potential game-changer for the prevention of AF development and recurrences? Examining these enquiries will improve the understanding of the present discoveries and emphasize the necessity for comprehensive lifestyle interventions to control AF. Future research should investigate the complex relationship between lifestyle factors and their impact on AF outcomes, both inside and beyond the PREDIMAR framework.