Effective treatment for heart failure with preserved ejection fraction (HFpEF) is an unmet need in cardiovascular medicine. The pathophysiological drivers of HFpEF are complex, differing depending on phenotype, making a one-size-fits-all treatment approach unlikely. Remarkably, sodium–glucose cotransporter 2 inhibitors (SGLT2is) may be the first drug class to improve cardiovascular outcomes in HFpEF. Randomised controlled trials suggest a benefit in mortality, and demonstrate decreased hospitalisations and improvement in functional status. Limitations in trials exist, either due to small sample sizes, differing results between trials or decreased efficacy at higher ejection fractions. SGLT2is may provide a class effect by targeting various pathophysiological HFpEF mechanisms. Inhibition of SGLT2 and Na+/H+ exchanger 3 in the kidney promotes glycosuria, osmotic diuresis and natriuresis. The glucose deprivation activates sirtuins – protecting against oxidation and beneficially regulating metabolism. SGLT2is reduce excess epicardial adipose tissue and its deleterious adipokines. Na+/H+ exchanger 1 inhibition in the heart and lungs reduces sodium-induced calcium overload and pulmonary hypertension, respectively.

BackgroundLVH is highly prevalent in patients with CKD and is independently associated with subsequent cardiovascular events.We hypothesized that adding systolic blood pressure values to LVH might differentiate different subgroups of patients at higher risk of cardiovascular events (CVE) and other adverse outcomes.MethodsRetrospective cohort study of 243 patients older than 60 years with stages 1-5 pre-dialysis CKD. LVH was assessed by electrocardiogram or echocardiogram.ResultsCardiovascular events occurred in 7 patients (10.3%) among those with SBP <130 and no LVH, 8 patients (10.5%) among those with SBP ≥130 and no LVH, 7 patients (21.2%) among those with SBP <130 and LVH and 25 patients (37.9%) among those with SBP ≥ 130 and LVH.On multivariate analyses, comparing to SBP < 130 and no LVH, the HR for CVE in those with SBP ≥ 130 and LVH was 4 (1.75, 10.3), p = 0.0007; 2.13 (0.71, 6.32) p = 0.16 in those with SBP <130 and LVH and 1.20 (0.42, 3.51) p = 0.72 in those with SBP ≥130 and no LVH.No significant differences were noted in changes in renal function and mortality rates among the groups.ConclusionThe combination of higher systolic blood pressure and LVH might identify older patients with CKD at higher risk of cardiovascular outcomes.