Frailty syndrome in heart failure: from definition to biomarkers

Abstract

Background. In an aging society, ensuring quality of life has become a major public health priority. Rising life expectancy and the high prevalence of cardiovascular risk factors have contributed to a global increase in heart failure (HF), currently affecting over 64 million people. At the same time, frailty syndrome (FS) – once considered a condition of the elderly – is now recognized in younger adults as well, categorized as early frailty (<65 years) and late frailty (≥65 years). FS is a multidimensional condition characterized by diminished physiological reserves and increased vulnerability to stressors, which significantly contributes to disability, hospitalizations, and mortality among patients with HF. This review aims to synthesize recent evidence on the definition, assessment, and prognostic value of biomarkers related to FS in individuals with HF. Materials and methods. This review analyzes 10 peer-reviewed studies published between 2022 and 2025, selected from PubMed, NCBI, and Google Scholar. The selected articles focused on frailty in the context of HF, including clinical definitions, diagnostic tools, and relevant biomarker profiles. Results. The concept of frailty has evolved from the Fried physical phenotype model to broader frameworks encompassing physical, psychosocial, and cognitive domains. Biomarkers with diagnostic and prognostic relevance in FS include inflammatory markers (IL-6, TNF-α, CRP), oxidative stress indicators, hormonal decline markers (testosterone, DHEA-S), and sarcopenia-related markers (myostatin, serum creatinine). Moreover, emerging research areas – such as adiponectin levels, epigenetic regulation, and gut microbiota composition – have been implicated in the pathophysiology of frailty in HF. Conclusions. Frailty syndrome is a major determinant of adverse outcomes in patients with HF, regardless of age. The identification of specific biomarkers offers promising avenues for early diagnosis, individualized risk stratification, and targeted interventions. Integrating biomarker-based assessments into routine clinical practice could enhance prognostic precision and alleviate the healthcare burden associated with HF and frailty.