Clinical Interventions in Aging

Biomarker-Guided Clinical Interventions in Geriatric Heart Failure: From Phenotyping to Practice

Heart failure (HF) affects over 64 million people worldwide and disproportionately burdens adults aged 65 and above, in whom clinical presentation, comorbidity burden, and physiological reserve differ markedly from younger patients. In this population, guideline-directed medical therapies — including renin-angiotensin-aldosterone system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors — produce variable effects on biomarkers of inflammation, neurohormonal activation, and cardiorenal stress, with evidence specific to older adults remaining limited. Understanding how clinical interventions modify these biological signals, whether changes in these biomarkers predict downstream outcomes such as mortality and HF hospitalization, and how biomarker-informed phenotyping can personalize therapeutic decision-making, represents one of the most pressing challenges in current geriatric cardiology.

The aging HF population is not homogeneous. Older adults with HF span a spectrum from the relatively fit patient with isolated left ventricular dysfunction to the frail, multimorbid individual with cardiorenal-hepatic syndrome and limited tolerance for aggressive pharmacotherapy. Emerging evidence indicates that circulating inflammatory markers (interleukin-6, CRP, GDF-15), cardiorenal biomarkers (cystatin C, NGAL), and neurohormonal indicators respond differentially to pharmacological, device-based, and rehabilitative interventions depending on the patient’s phenotypic subtype. Identifying which interventions most effectively normalize these biomarkers — and which patient subgroups benefit most — has direct implications for risk stratification and treatment personalization in older adults.

This Article Collection invites original research, systematic reviews, and narrative reviews examining how clinical interventions in older adults with HF influence biomarker profiles, phenotypic trajectories, and patient outcomes. Relevant subtopics include: the effects of pharmacological therapies (SGLT2 inhibitors, ARNIs, mineralocorticoid receptor antagonists) on inflammatory, neurohormonal, and cardiorenal biomarkers in patients aged 65 and above; the impact of device-based therapies (ICD, CRT, LVAD) and structured cardiac rehabilitation on biomarker levels and phenotypic classification in geriatric HF cohorts; biomarker-guided treatment titration and serial monitoring strategies in older adults with acute or chronic HF; machine learning and phenotyping approaches that identify which patient subgroups derive the greatest benefit from specific interventions; sex-, ethnicity-, and geography-specific variation in biomarker responses to clinical interventions; and real-world multicentred data on intervention outcomes in older adults with HF, including frail and multimorbid subgroups. Studies from diverse geographic regions, including Asia, Europe, and the Americas, are particularly encouraged.