Inflammasome pathway component expressions in myocardial samples of advanced heart failure patients treated with novel heart failure pharmacotherapies.

Nagy, Dávid and Onódi, Zsófia and Kovács, Andrea and Bálint, Tímea and Horváth, Zoltán and Oláh, Attila and Sayour, Alex Ali and Barta, Bálint András and Ferdinandy, Péter and Radovits, Tamás and Merkely, Béla and Varga, Zoltán and Ruppert, Mihály (2026) Inflammasome pathway component expressions in myocardial samples of advanced heart failure patients treated with novel heart failure pharmacotherapies. INTERNATIONAL JOURNAL OF CARDIOLOGY, 462. No. -134686. ISSN 1874-1754

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Abstract

BACKGROUND The inflammasome pathway has been implicated in the progression of heart failure (HF). Preclinical studies suggest that angiotensin receptor-neprilysin inhibitor (ARNi) and sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapies may attenuate inflammasome activation, yet evidence in the failing human myocardium remains sparse. Hence, we evaluated the associations between ARNi and SGLT2i therapies and myocardial priming of inflammasome pathway components in explanted hearts from heart transplantation (HTX) recipients. METHODS Biobank samples from the left ventricular myocardium of 104 HTX recipients were analyzed. The mRNA and protein expression of inflammasome-related targets (absent in melanoma 2 [AIM2], NLR family pyrin domain containing 3 [NLRP3], caspase-1, gasdermin D, and nuclear factor kappa-light-chain-enhancer of activated B cells [NF-κB]) were quantified using qRT-PCR and Western blotting. Multivariable linear regression models were applied to assess the relationships between inflammasome component expression and clinical variables, including treatment with ARNi and SGLT2i. RESULTS ARNi and SGLT2i therapies were associated with lower mRNA expression of AIM2, NLRP3, caspase-1, and NF-κB in univariate analyses. However, after adjustment for clinical covariates, these associations with inflammasome-related transcripts were no longer statistically significant. In multivariable models, only female sex, diabetes, time since heart transplantation, and serum potassium concentration remained associated with myocardial inflammasome pathway expression. CONCLUSIONS In myocardial samples from patients with advanced HF, no clear differences in the expression of selected inflammasome priming-related targets were observed between treatment eras before and after the introduction of ARNi and SGLT2i therapies, despite their experimentally suggested anti-inflammatory effects, warranting further investigation.

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