The role of anti-diabetic drugs on the extent of post-BAriatric surgery CARDIac reverse remodelling (BACARDI)

Abstract

Abstract Introduction: Heart failure (HF) affects over 26M people, with its prevalence rising with ageing and other comorbidities, such as obesity. Obesity induces cardiac remodelling, often asymptomatic. Bariatric surgery leads to great weight loss, being associated with variable grades of cardiac reverse remodelling (RR). Some anti-diabetic drugs demonstrate an unclear impact on cardiac function. Thus, we propose to investigate the impact of bariatric surgery on cardiac, metabolic, and adipose tissue RR and the influence of glucagon-like peptide-1 receptor agonists (GLP1-RA) or sodium-glucose transport protein 2 inhibitors (SGLT2i) administered before surgery on these parameters. Methods: We recruited consecutive adults up to 65 years with preserved ejection fraction scheduled for bariatric surgery at Unidade Local de Saúde de São João from October 2024 to April 2025. A transthoracic echocardiography, a pulse wave velocity measurement, body composition analysis, and a 6-minute walk test were performed at baseline (immediately before the surgery, T0) and 3 months after bariatric surgery (T1), as well as clinical anthropometric data collection, quality of life assessment, and a dietary characterization through questionnaire application. Visceral adipose tissue was collected during bariatric surgery for histomorphometric analysis. The study sample was divided into two groups: those receiving GLP1-RA or SGLT2i therapy (BARD group) and those not receiving it (CTRL group). Data distribution was checked by histograms and Shapiro-Wilk; results are mean±SD or median (P25-P75). Comparisons were through independent t-tests (Welch if needed), paired t-tests for paired data, Mann-Whitney for nonnormal variables, chi-square for categorical data, and mixed-effects models for longitudinal analyses; p<0.05. Results: Nineteen obese participants (9 females and 10 males; mean age 50 ± 10 (years) were included, comprising 8 in the BARD group and 11 in the CTRL group. Regarding the cardiac and vascular RR, no significant changes were observed following bariatric surgery. However, the BARD group showed a higher relative wall thickness (RWT) at baseline compared to the CTRL group (p = 0.020). At follow-up (T1) a significant weight loss was documented (Body Mass Index (BMI): 46 ± 7 kg/m2 to 38 ± 7 kg/m2, p<0.001), associated with marked decreases in total fat mass (−29%, p<0.001), visceral fat area (−28%, p=0.003), intracellular (−10%, p<0.001) and extracellular water (−9%, p=0.014), and resting metabolic rate (−8%, p=0.001), no significant differences between study groups being registered. Similarly, no significant changes were observed in the total distance walked neither from baseline to T1, nor between groups, despite a significant strong correlation with LV mass reduction (r = −0.984, p = 0.016), which goes along with a significant improvement at T1 of the oxygen saturation (+3%, p=0.030) and decreased dyspnoea sensation (-2 points, p=0.001), both at the end of exercise. In like manner, an improvement in physical limitations (+22 points, p = 0.001) assessed by the Kansas City Cardiomyopathy Questionnaire was observed, as well as in quality of life (+29 points, p<0.001) and other domains; no significant group differences were documented. Only a small number of participants showed good adherence to the Mediterranean diet (5%), but the level of adherence to it also did not show any significant correlation with cardiac structure/function, body composition, visceral adipose tissue fibrosis percentage (that was higher in the BARD group - p= 0.042 - despite no cross-sectional area difference with CTRL group). Conclusions: Despite significant symptomatic and metabolic improvements after 3 months of bariatric surgery, no significant effects were observed on cardiac or vascular RR, independent of antidiabetic drug use. However, a trend toward regression of concentric hypertrophy was observed, as indicated by a reduction in RWT, although this did not reach statistical significance. Interestingly, participants receiving GLP1-RA or SGLT2i therapy before bariatric surgery exhibited a significant reduction in RWT at three months post-surgery. In contrast, prior treatment with GLP1-RA or SGLT2i was also associated with an increase in visceral adipose tissue fibrosis compared with participants who were not receiving such therapy