Intensive hypoglycemic treatment is the strongest preventive strategy against the development of microvascular complications of type 2 diabetes (T2DM), including diabetic nephropathy. However, some antidiabetic drugs, i.e. sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) have an additional renoprotective effect beyond glucose control by itself. Similar, both SGLT-2i and GLP1-RA have been demonstrated to decrease the risk of adverse cardiovascular (CV) events in CV outcome trials. Nevertheless, there are relevant differences in CV and renal effects of SGLT-2i and GLP1-RA. First, SGLT2i reduced the incidence and progression of albuminuria and prevented loss of kidney function, while predominant renal benefits of GLP1-RA were driven by albuminuria outcomes. Second, the risk of heart failure (HF) hospitalizations decreased on SGLT2i but not on GLP1-RA, which gives priority to SGLT2i in T2DM and HF, especially with depressed EF. Third, either GLP1-RA (reducing predominantly atherosclerosis-dependent events) or SGLT-2i, should be used in T2DM and established atherosclerotic CV disease (ASCVD) or other indicators of high CV risk. In this review, we have briefly compared clinical practice guidelines of the American Diabetes Association (2020 and 2021 versions), Polish Diabetes Association (2020) and the European Society of Cardiology/European Association for the Study of Diabetes (2019), with a focus on the choice between SGLT-2i and GLP1-RA in patients with diabetic kidney disease.

B a c k g r o u n d: A novel paradigm of diastolic heart failure with preserved ejection fraction (HFpEF) proposed the induction of coronary microvascular dysfunction by HFpEF comorbidities via a systemic pro-infl ammatory state and associated oxidative stress. Th e consequent nitric oxide deficiency would increase diastolic tension and favor fi brosis of adjacent myocardium, which implies not only left ventricular (LV), but all-chamber myocardial stiff ening. Our aim was to assess relations between low-grade chronic systemic infl ammation and left atrial (LA) pressure-volume relations in real-world HFpEF patients.

Me t h o d s: We retrospectively analyzed medical records of 60 clinically stable HpEFF patients in sinus rhythm with assayed high-sensitive C-reactive protein (CRP) during the index hospitalization. Subjects with CRP >10 mg/L or coexistent diseases, including coronary artery disease, were excluded. LV and LA diameters and mitral E/E’ ratio (an index of LA pressure) were extracted from routine echocardiographic 46 Cyrus M. Sani, Elahn P.L. Pogue, et al. records. A surrogate measure of LA stiff ness was computed as the averaged mitral E/e’ ratio divided by LA diameter.

R e s u l t s: With ascending CRP tertiles, we observed trends for elevated mitral E/e’ ratio (p <0.001), increased relative LV wall thickness (p = 0.01) and higher NYHA functional class (p = 0.02). Th e LA stiffness estimate and log-transformed CRP levels (log-CRP) were interrelated (r = 0.38, p = 0.003). On multivariate analysis, the LA stiff ness index was independently associated with log-CRP (β ± SEM: 0.21 ± 0.07, p = 0.007) and age (β ± SEM: 0.16 ± 0.07, p = 0.03), which was maintained upon adjustment for LV mass index and relative LV wall thickness.

C o n c l u s i o n s: Low-grade chronic infl ammation may contribute to LA stiff ening additively to age and regardless of the magnitude of associated LV hypertrophy and concentricity. LA stiff ening can exacerbate symptoms of congestion in HFpEF jointly with LV remodeling.