Ischemic heart disease (IHD) remains the leading cause of chronic heart failure (HF) worldwide, yet the biological processes underlying this transition are not fully elucidated. Growing evidence indicates that chronic, low-grade inflammation acts as a pivotal link between ischemic injury and progressive myocardial dysfunction. Our review is the most up-to-date and structured synthesis on the pathophysiological pathways, biomarkers, and therapeutic implications of subclinical inflammation in patients with IHD at risk of developing HF. Following acute or repetitive ischemic episodes, persistent immune activation—mediated through interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α)—promotes endothelial dysfunction, microvascular instability, and extracellular matrix remodeling. These mechanisms culminate in ventricular stiffness, diastolic impairment, and adverse structural remodeling, even when left ventricular ejection fraction is preserved. Biomarkers such as Galectin-3, cancer antigen 125 (CA125), and high-sensitivity C-reactive protein (hsCRP) provide valuable insight into the interplay between fibrosis, congestion, and systemic inflammatory load, supporting early detection of subclinical myocardial injury. Advanced imaging modalities, including strain echocardiography and cardiac magnetic resonance imaging (MRI) mapping, enhance the phenotypic characterization of inflammatory cardiomyopathy. Understanding and targeting these inflammatory pathways may open new avenues for precision-based prevention and treatment, ultimately improving outcomes across the IHD–HF continuum.

Background/Objectives: Advanced heart failure (HF) carries a high symptom burden and mortality, and identifying the right time for palliative and advanced-therapy discussions remains difficult. We systematically reviewed the prognostic value of serological biomarkers, echocardiographic indices, and patient-reported outcomes (PROs) in advanced HF. Methods: PubMed, Scopus, Web of Science, and the Cochrane Library were searched on 1 June 2026 for studies published within the prior 10 years, following PRISMA 2020 (PROSPERO CRD420261505929). Risk of bias was assessed with the Newcastle–Ottawa Scale and certainty of evidence with GRADE. Hazard ratios (HRs) for all-cause mortality were pooled with random-effects models within pathophysiologically defined serological subgroups; markers with opposing prognostic directions were synthesized narratively. Results: Of 3866 records, 37 studies (approximately 31,849 patients) were included; 29 (78%) were at low risk of bias. The pooled HR was 1.35 (95% CI 1.06–1.74; k = 4; I² = 92%) for neurohormonal/congestive markers; exploratory two-study estimates were 1.75 (1.50–2.04; I² = 6%) for renal/cardiorenal and 2.17 (0.85–5.52; I² = 86%) for inflammatory-nutritional markers. GRADE certainty was Low for the renal/cardiorenal estimate and Very Low for the other two, and funnel-plot asymmetry suggested small-study effects. Echocardiographic and PRO markers were individually associated with prognosis but showed opposing directions within outcome categories and were not pooled. Conclusions: Serological, echocardiographic, and patient-reported markers each carry prognostic information in advanced HF, but the pooled estimates are exploratory. Most studies assessed mortality or hospitalization rather than palliative or advanced-therapy decisions; relevance to such decisions is interpretive and requires prospective confirmation.