Pre-Existing Heart Failure, Biomarker Profiles, and Patients’ Vulnerability in Hospitalized COVID-19: A Biomarker-Driven Risk Framework

<b>Background/Objectives</b>: Heart failure (HF) has been associated with adverse outcomes in coronavirus disease 2019 (COVID-19), but it remains unclear whether HF independently predicts sepsis and mortality once inflammatory and cardiac biomarkers are considered. <b>Methods</b>: This single-center retrospective cohort analysis included 127 adult patients hospitalized with laboratory-confirmed COVID-19 at a tertiary infectious diseases hospital between March 2020 and December 2024. Pre-existing HF was defined based on cardiology records and chronic HF therapy. Baseline assessments included clinical characteristics, echocardiography, and biomarkers (NT-proBNP, high-sensitivity troponin, C-reactive protein [CRP], interleukin 6 [IL-6], procalcitonin, and D-dimer) measured within 24 h of admission. Primary outcomes were sepsis and all-cause mortality (in-hospital or 30-day). Independent associations with sepsis and mortality were examined using multivariable logistic regression incorporating demographic factors, major comorbidities, baseline disease severity, and inflammatory and cardiac biomarkers. <b>Results</b>: Of 127 patients (mean age 70.1 ± 14.8 years, 63.8% male), 30 (23.6%) had pre-existing HF. Patients with preexisting heart failure exhibited significantly reduced left ventricular ejection fraction and higher admission levels of NT-proBNP and high-sensitivity troponin, accompanied by a substantially increased burden of in-hospital cardiovascular complications (53.3% vs. 14.4%, <i>p</i> < 0.001). However, sepsis (6.7% vs. 7.2%, <i>p</i> = 1.000) and total mortality (20.0% vs. 17.5%, <i>p</i> = 0.971) did not differ significantly between HF and non-HF groups. In multivariable analyses, HF was not independently associated with sepsis (adjusted odds ratio [aOR] 0.78, 95% confidence interval [CI] 0.05-12.34, <i>p</i> = 0.855) or mortality (aOR 0.63, 95% CI 0.16-2.46, <i>p</i> = 0.506). By contrast, higher CRP (aOR 1.01 per 1 mg/L, 95% CI 1.00-1.01, <i>p</i> = 0.007), IL-6 (aOR 1.01 per 1 pg/mL, 95% CI 1.00-1.01, <i>p</i> = 0.025), and high-sensitivity troponin (aOR >999, 95% CI 138->999, <i>p</i> = 0.001) were independently associated with mortality. <b>Conclusions</b>: In hospitalized COVID-19 patients, pre-existing HF identifies a subgroup with heightened cardiac biomarker activation and a substantially higher burden of cardiovascular complications but does not associate with sepsis or short-term mortality in this cohort after adjustment for inflammatory and cardiac biomarkers. Mortality risk appears to be driven primarily by systemic inflammation and acute myocardial injury, as reflected by CRP, IL-6, and high-sensitivity troponin. These findings support a biomarker-driven approach to risk stratification in COVID-19, in which dynamic inflammatory and cardiac injury profiles provide more prognostic information than HF status alone, while still warranting intensified cardiovascular surveillance in patients with HF.