Background: Elderly patients with heart failure with reduced ejection fraction (HFrEF) who experience worsening heart failure (wHF) remain at high residual risk despite optimal medical therapy (OMT), and data on cognitive function and comprehensive geriatric assessment (CGA) in this setting are lacking. This study evaluated the association between 12-month treatment with vericiguat and changes in cardiac, functional and geriatric parameters in elderly patients with recent wHF. Methods and results: In this single-center prospective observational study, 55 patients (45 men, mean age 76.4 ± 5.1 years) with HFrEF on OMT and a recent episode of wHF were treated with vericiguat and followed for 12 months. Clinical assessment, CGA and echocardiography including speckle-tracking were performed at baseline, 6, and 12 months. At 12 months, the mean vericiguat dose was 5.5 ± 2.9 mg/day. NT-proBNP levels decreased from 980 (467–2106) to 654 (274–1762) pg/mL (p < 0.0001), while left ventricular ejection fraction increased from 36.8 ± 3.1% to 43.4 ± 5.7% (p < 0.0001). Global longitudinal strain improved from −9.2 ± 1.7% to −11.5 ± 2.1% (p = 0.008), with parallel improvements in right ventricular function and pulmonary pressures. Cognitive performance improved (MMSE 25.1 ± 1.7 to 26.2 ± 2.1 points, p < 0.0001), as did depressive symptoms (GDS 7.8 ± 2.0 to 5.4 ± 1.6 points, p < 0.0001), physical performance (SPPB 6.7 ± 1.1 to 8.4 ± 0.9 points, p < 0.0001), and gait speed (0.70 ± 0.10 to 0.83 ± 0.06 m/s, p < 0.0001). Conley score decreased from 5.2 ± 2.3 to 2.4 ± 1.8 points (p < 0.0001), suggesting a lower risk of falls. Loop diuretic and MRA use were significantly reduced during follow-up. Conclusions: In this elderly HFrEF cohort with recent wHF on contemporary OMT, 12-month treatment with vericiguat was associated with consistent improvements in cardiac structure and function, biomarkers, and multidimensional geriatric status. These hypothesis-generating findings support the integration of CGA into future controlled studies of vericiguat in frail older patients with HFrEF. Given the observational design and lack of a control group, causal inference is not possible.

BACKGROUND: Heart failure (HF) is a clinical syndrome that involves multiple interconnected pathways. Circulating biomarkers in HF emerged as powerful tools for risk stratification, diagnostic confirmation, prognostic assessment, and monitoring of treatment efficacy. The aim of the present study was to evaluate circulating levels of biomarkers in elderly patients with HF improved ejection fraction, previously with left ventricular ejection fraction (LVEF) <40%, after 6 months of drug therapy optimisation. METHODS: We enrolled 100 HFimpEF outpatients. All patients underwent medical history and physical examination, at the baseline and after 6 months of follow-up. The serum values of circulating biomarkers were assessed with ELISA test. Proteomic analysis was performed on serum samples collected from a subset of 13 patients at baseline and after 6 months of follow-up. RESULTS: At follow-up, we observed significant improvements in glycometabolic, renal and inflammatory profile (p<0.001). Proteomic analysis revealed selective changes in key cardiovascular (CV)-related proteins, such as Insulin-like growth factor-binding protein 4 (IBP4) Thrombospondin4 (TSP4), Intercellular adhesion molecule 1 (ICAM1), Syndecan-4 (SDC4). CONCLUSIONS: This study demonstrates significant improvements across multiple CV biomarkers, after 6 months of therapy optimization, in HFimpEF patients, providing evidence for comprehensive therapeutic effects targeting inflammation, oxidative stress, neurohormonal activation, and thrombotic risk.