Imidazoline receptor agonists and heart failure: a modern perspective. Reconsidering concepts?

Abstract

Heart failure with preserved ejection fraction (HFpEF) accounts for at least half of all cases of heart failure (HF) and is closely associated with hypertension (HTN), metabolic diseases, and chronic kidney disease. According to the PRIORITY-HF registry study, hypertension was detected in 94,2% of patients with HFpEF, obesity in 49,9%, type 2 diabetes in 29,7%, and chronic kidney disease in 49,7%. A body mass index higher than 30 kg/m 2 was recorded in 47,9% of patients. The article discusses the main pathogenetic mechanisms of HFpEF, including left ventricular pressure overload, increased vascular stiffness, visceral obesity, chronic low-grade inflammation, adipokine profile dysregulation, and sympathetic nervous system hyperactivation. Particular attention is paid to the cardiometabolic phenotype of HFpEF, in which the combination of HTN, obesity, insulin resistance, and systemic inflammation determines the progression of diastolic dysfunction and complicates the achievement of target blood pressure levels. The potential role of imidazoline receptor agonists, primarily moxonidine, as a component of personalized antihypertensive therapy in selected patients with hypertension and HF with EF is rationaled. The antihypertensive and metabolic effects of moxonidine are discussed, including a reduction in sympathetic activity, improved tissue sensitivity to insulin, and its effects on leptin and chronic inflammation parameters. The historical limitations of moxonidine use in heart failure associated with the MOXCON study are discussed, as well as the impossibility of directly extrapolating these data to patients with class I-II HFpEF. Current data allow moxonidine to be considered a pathogenetically justified therapeutic option in some patients with HTN, the cardiometabolic phenotype of HFpEF, and without severe heart failure decompensation.