Effects on mitral and tricuspid valve regurgitation after 6 months of treatment with SGLT2 inhibitors in patients with chronic heart failure

Background: Sodium-GLucose coTransporter 2 inhibitors (SGLT2i) have revolutionized the therapeutic management of chronic heart failure (CHF) with a remarkable reduction of mortality and an improvement of quality of life. Moreover, it was highlighted their bene cial role on adverse cardiac remodelling. The effects on mitral and tricuspid valve function of these drugs should be further explored. Purpose: The aim of this study was the investigation of the effects on mitral and tricuspid valve function after 6 months of treatment with SGL2i in patients with CHF. Methods: We conducted an observational, perspective, monocentric study enrolling 169 patients with CHF from December 2020 to March 2024 in a tertiary referral hospital. For each patient, anamnestic, laboratory, clinical and echocardiographic data were collected. Each patient underwent a transthoracic echocardiographic evaluation before SGLT2i initiation and after 6 months of follow-up by two cardiologists with expertise. The prescription of SGLT2i was made according to the European guidelines on Heart Failure. The examination was focused on the assessment of mitral and tricuspid valve regurgitations using a semi-quantitative rating scale and biventricular volumes and function. Results: The median age of the study population was 66 years (IQR 17) with a clear prevalence of male sex (82% of cases). More than 70% of subjects presented a dilated left ventricular (LV) phenotype, with an ischaemic aetiology in more than one third of cases. After 6 months of treatment was found a statistically signi cant reduction of Body Mass Index (p<0.001), an improvement in NYHA class (p=0.006), an increase of haemoglobin levels (p=0.001) and a decrease in loop diuretics usage (p=0.003). Regarding echocardiographic parameters, the LV end-diastolic volume decreased from 142 ml (IQR 67) to 135 ml (IQR 75) (p<0.001). Similarly, was pointed out a reduction of the LV end-systolic volume from a value of 94 ml (IQR 56) to a 82 ml (IQR 55) (p<0.001). Moreover, the LV ejection fraction improved from 35% (IQR 12) to 38% (IQR 14) (p<0.001). In about one quarter of cases mitral valve regurgitation was decreased, with a statistically signi cant reduction of moderate and severe regurgitations from 27% at baseline to 22% in the follow up (p=0.035). On the contrary, there were no statistically signi cant variations in the degree of tricuspid regurgitation (13% of cases with moderate and severe grade at baseline vs 14% in the follow up, p=0.774). Moreover, no relevant changes were observed in the systolic function of the right ventricle (p=0.675). Conclusions: SGLT2s may have a bene cial effect on functional mitral regurgitation, leading to a reduction in its degree. This could be explained by the well-known diuretic effect of these drugs together with a positive role on adverse remodelling of the left ventricle.