ARNI and SGLT2i therapies were independently associated with reduced interstitial myocardial fibrosis in advanced heart failure patients, but not with changes in inflammasome pathway proteins.
Observational (n=93)
Do ARNI and SGLT2i therapies reduce myocardial fibrosis and inflammasome pathway proteins in advanced HF patients undergoing heart transplantation?
ARNI and SGLT2i therapies are associated with reduced myocardial fibrosis in advanced heart failure patients, providing mechanistic insight into their clinical benefits.
Abstract Introduction Novel heart failure (HF) pharmacotherapies such as angiotensin receptor-neprilysin inhibitors (ARNI) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve HF survival. Behind this clinical benefit, the inhibition of myocardial inflammation (such as the inflammasome pathway) and fibrosis are postulated based on previous experimental results, but human evidence in this area remain limited. Purpose We aimed to measure the antifibrotic action and the inhibition of the inflammasome pathway by ARNI and SGLT2i therapies in myocardial biobank samples of advanced HF patients undergoing heart transplantation (HTX). Methods 93 advanced HF patients who received either ARNI or angiotensin converting enzyme inhibitor (ACEi) treatment along with optional SGLT2i therapy and optimal HF medical therapy (including a beta-blocker and mineralocorticoid receptor antagonist) for at least 3 months prior to HTX were enrolled in our analysis. Left ventricular myocardial samples from the explanted hearts of these patients were harvested during HTX. The myocardial mRNA expression of fibrotic markers and inflammasome pathway proteins were assessed by qRT-PCR. Interstitial fibrosis area was measured by histological analysis. The measured outcomes were adjusted to other clinical parameters in multivariable linear- or beta regression models. Results Both ARNI and SGLT2i therapies were independently associated with reduced interstitial myocardial fibrosis in univariate and multivariable regression models as well. In SGLT2i-treated patients, reduced mRNA levels of matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinases 2 (TIMP2) were observed in adjusted models. However, neither ARNI, nor SGLT2i therapies were associated with significant changes in the examined inflammasome protein genes (absent in melanoma 2, caspase-1, Gasdermin D, nuclear factor kappa-light-chain-enhancer of activated B cells, stimulator of interferon genes). Conclusions ARNI and SGLT2i therapies are associated with reduced myocardial fibrosis in myocardial samples of advanced HF patients, but no significant associations can be observed with the myocardial gene expression of inflammasome pathway proteins.
Nagy et al. (Fri,) conducted a observational in Advanced heart failure (n=93). ARNI and SGLT2i therapies vs. ACEi and/or no SGLT2i therapy was evaluated on Interstitial fibrosis area and myocardial mRNA expression of fibrotic markers and inflammasome pathway proteins. ARNI and SGLT2i therapies were independently associated with reduced interstitial myocardial fibrosis in advanced heart failure patients, but not with changes in inflammasome pathway proteins.