WEIGHT LOSS REVERSES ADVERSE STRUCTURAL, ELECTROPHYSIOLOGICAL AND AUTONOMIC REMODELLING IN OBESITY

Abstract Background Obesity is a global health problem that associates with cardiovascular disease and is an independent risk factor for cardiac arrhythmias. We previously showed QTc interval prolongs with increasing adiposity at a population level amongst the UK Biobank cohort, and that cardiac myocytes exhibit slower conduction in vitro when incubated with human epicardial vs subcutaneous adipose tissue. To study the clinical reversibility of the proarrhythmic substrate in obesity, we characterised structural, electrophysiological and autonomic remodelling in arrhythmia-free obese patients pre- and post-bariatric surgery. Methods Sixteen arrhythmia-free obese patients (BMI 46.7 ± 5.5 kg/m2) and sixteen age- and sex-matched lean individuals (BMI 22.8 ± 2.6 kg/m2) were enrolled. Participants underwent non-invasive electrocardiographic imaging, comprising cardiac MRI and 256-lead body surface ECGs to mathematically compute >2000 epicardial electrograms using customised software. Results Obese individuals had greater epicardial fat and left ventricular mass, blunted heart rate variability, slower atrial conduction and steeper ventricular repolarisation gradients compared to lean participants. Bariatric surgery was associated with reduction in epicardial fat (68.7cm3 vs 64.5cm3, p = 0.0010), left ventricular mass (33 g/m2.7 vs 25 g/m2.7, p < 0.0005) and spatial ventricular repolarisation gradients (26 mm/ms vs 19 mm/ms, p = 0.0009). Heart rate variability, quantified by standard deviation of successive differences of RR intervals, also improved following post-surgery (18.7 ms vs 25.9 ms, p = 0.017). Computational modelling showed obese hearts had reduced vulnerability to unidirectional block, delayed spiral-wave break-up and less complex re-entry patterns post-surgery. Conclusion Obesity is associated with adverse but reversible structural, electrophysiological and autonomic remodelling. These data have important public health implications for weight thresholds for bariatric surgery and weight loss strategies.