{
  "abstract": "Background Following several landmark trials, sodium glucose co-transport (SGLT) 2 inhibitors, have been established as a guideline directed therapy for heart failure (HF). Much remains unclear regarding their mechanism of action with current evidence implicating involvement of inflammatory, autophagic and anti-fibrotic pathways.Aim We therefore sought to evaluate the effects of SGLT2 inhibition on cardiac biomarkers, myocardial remodeling and patient reported outcomes in heart failure.Methods This was a 26-week, single-arm prospective evaluation of the effects of SGLT2 inhibition on cardiac biomarkers, myocardial remodeling and patient reported outcomes in patients with heart failure. Baseline echocardiography, serum analysis (standard care and novel biomarkers) and QoL metrics were assessed prior to SGLT2i therapy and at 26-week follow-up. Novel biomarkers were analysed using enzyme-linked immunosorbent assays. Data were analysed using SPSS (IBM SPSS Statistics, Version 28.0). Clinical Trials.gov identifier: NCT06140251.Results Forty-six patients were recruited with forty patients undergoing novel biomarker analysis (mean age 67.2±8.2years: 68.3% female). Mean LV ejection fraction (LVEF) at baseline was 45.3+/9.8% (ischaemic aetiology: 40.0%, diabetic: 5%). At a median follow-up of 196 days, sSt2 fell significantly (mean difference -13.5pg/ml [95% CI: -17.9 to - 8.9: p<0.001]), with no significant change in IL1β, IL4, IL6 or IGFBP1 (all p=ns) ( table 1 ). Interestingly, delta change in IL-6 modestly correlated with change in global longitudinal strain (GLS) (%) (r=-0.43, p=0.012). Change in GLS (%) was not correlated with other novel cardiac biomarkers nor were there between group differences when delineated by the presence of reverse cardiac remodeling at six months (Figure 1).Conclusion In our cohort we found that sSt2, a protein implicated in cardiac fibrosis, was suppressed by SGLT2i. Additionally, we observed that suppression of IL-6, a marker of inflammation, correlated with improvement in GLS. These data support the implication of SGLT2i in suppression of fibrotic and inflammatory pathways.Abstract 4 Table 1Change in novel biomarkers following SGLT2 inhibitor therapy. Data presented as mean (range) with differences in means assessed using a paired two-tailed t-test with significance defined as p < 0.05. *An insufficient number of patients in our cohort had detectable levels of IL-1B at follow-up, therefore precluding a paired analysis. SGLT2i = sodium-glucose co-transport 2 inhibitor; sST2 = soluble suppression of tumorigenicity 2 protein; IGFBP1 = insulin-like growth factor-binding protein; IL-1B = interleukin-1 beta; IL-4 = interleukin-4; IL-6 = interleukin-6Abstract 4 Figure 1Scatter plot demonstrating positive correlation between delta in LV GLS (%) and IL-6 following SGLT2 inhibition. Bivariate analysis was performed using pearson correlation with a two-sided significance level defined as P value < 0.05. δ = delta; SGLT2 = sodium-glucose co-transporter 2; IL-6 = interleukin-6; GLS = global longitudinal strain.",
  "authors": [
    {
      "affiliations": [
        "Royal Victoria Hospital, Belfast, UK"
      ],
      "name": "P Savage"
    },
    {
      "affiliations": [
        "Royal Victoria Hospital, Belfast, UK"
      ],
      "name": "K Linden"
    },
    {
      "affiliations": [
        "Royal Victoria Hospital, Belfast, UK"
      ],
      "name": "C Watson"
    },
    {
      "affiliations": [
        "Queens University Belfast, Belfast, UK"
      ],
      "name": "D Grieve"
    },
    {
      "affiliations": [
        "Royal Victoria Hospital, Belfast, UK"
      ],
      "name": "L Dixon"
    }
  ],
  "title": "4 Investigation of biomarker response to SGLT2 inhibition in heart failure (SiN-HF study)",
  "uid": "3c2bf327-5fc5-5047-bab4-5a92798e539e"
}