SGLT2 inhibitors improved WHO functional class, reduced signs of right heart failure (OR 3.46), and lowered echocardiographic pulmonary hypertension probability in HFrEF patients.
Do SGLT2 inhibitors improve functional class, right heart failure signs, echocardiographic probability of pulmonary hypertension, and biological markers in patients with HFrEF?
SGLT2 inhibitors improve functional capacity, right ventricular function, and echocardiographic probability of pulmonary hypertension in HFrEF patients, potentially mediated by downregulation of activin and miR-1306-5p pathways.
Absolute Event Rate: 0% vs 0%
Abstract Background Pulmonary hypertension (PH) often complicates heart failure (HF) but can hardly be addressed therapeutically. Whether sodium-glucose cotransporter 2 inhibitors (SGLT2i) positively impact on HF-associated PH is unknown. Omics may lead to the discovery of novel therapeutic targets for HF and PH. Aims To evaluate the impact of SGLT2i - compared to conventional anti-HF therapy - on mid-term clinical and echocardiographic outcomes and to relate them to potential biological effects, including changes in senescence and oxidative stress markers (telomere length, mitochondrial DNA), proteomic and miRNA expression profiles. Methods In an observational series of seventy-four patients with HF and reduced ejection fraction (HFrEF) patients were divided into two groups receiving (T=0) either 10 mg/day the SGLT2i dapagliflozin or empagliflozin on top of conventional anti-HF therapy (gliflozin group G), or a no-gliflozin anti-HF therapy (no-gliflozin group). Plasma samples from the gliflozin and the no-gliflozin groups were profiled by untargeted proteomics. Results Compared to the no-gliflozin group, the gliflozin group at follow-up had better World Health Organization functional class (WHO-FC Δ 0.03±1,5 vs 1.1±1, p=0.001), lesser clinical signs of right heart failure (odds ratio OR 3.46; 95% CI 1.2-9.8; p=0.023) and a lower echocardiographic probability of PH (1.88±0.89 vs 1.4±0.62, p=0.017). In the gliflozin group, several biological pathways were triggered (p-value 10-3), such as those related to the T-lymphocyte immune response, chemotaxis of monocytes, leukocytes and phagocytes. Importantly, the gliflozin group featured a downregulation of the activin and miR-1306-5p signaling pathways, which are now emerging as novel therapeutic targets in pulmonary arterial hypertension (PAH). Conclusions In HF patients, SGLT2i improve functional capacity and right ventricular function and reduce the echocardiographic probability of PH. The activin and miR-1306-5p pathways are overactivated in HF patients and serum levels of such biomarkers are reduced by SGLT2i. SGLT2i may thus be be an additional therapeutic tool in patients with HF-associated PH.
Madonna et al. (Sat,) reported a other. SGLT2 inhibitors improved WHO functional class, reduced signs of right heart failure (OR 3.46), and lowered echocardiographic pulmonary hypertension probability in HFrEF patients.