THE IMPORTANCE OF CYTOMEGALOVIRUS INFECTION AND MOLECULAR BIOMARKERS IN PREDICTING ADVERSE OUTCOMES IN PATIENTS WITH CHRONIC HEART FAILURE

The purpose of the study. To compare the prognostic significance of cytomegalovirus (CMV) activity indicators and molecular biomarkers (N-terminal pro-brain natriuretic peptide (NT-proBNP), soluble ST2, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β)) in assessing the risk of developing adverse cardiovascular events in patients with chronic heart failure (CHF) over 24 months of observation.

Material and Methods. The study included 151 patients with functional classes II–IV CHF, aged 50–70 years, with subsequent prospective observation for 24 months. The endpoint was a composite defined as hospitalization for CHF decompensation and the occurrence of adverse clinical events (cardiovascular death, nonfatal myocardial infarction or acute cerebrovascular accident, and pulmonary embolism) during the 24-month observation period. Blood cytomegalovirus DNA was detected using polymerase chain reaction at study entry. NT-proBNP levels were determined by immunochemiluminescent analysis, and soluble ST2, TNF-α, and IL-1β levels were determined by solid-phase enzyme-linked immunosorbent assay.

Results. The highest risk of death (OR = 8,57; 95% CI = 1,98-37,1; p = 0,004) and the occurrence of a combined endpoint event (OR = 3,17; 95% CI = 1,78–5,64; p < 0,001) was observed in CMV-seropositive patients. Other markers demonstrated a lower hazard ratio for developing a fatal outcome within 24 months from 1,14 (95% CI = 1,06–1,24; p < 0,001) for IL-1β to 1,42 (95% CI = 1,21–1,66; p < 0,001) for soluble ST2; for the combined endpoint – from 1,1 for IL-1β (95% CI = 1,05–1,15; p < 0,001) to 1,30 for soluble ST2 (95% CI = 1,18–1,42; p<0,001). Multivariate analysis revealed an increased risk of death (OR = 1,24; 95% CI = 1,12–1,38; p < 0,001) and the occurrence of a composite endpoint event (OR = 1,12; 95% CI = 1,07–1,18; p < 0,001) with each 100 copies/mL increase in CMV DNA. Viral load had a greater predictive power than factors such as gender, age, atrial fibrillation, CHF functional class, and TNF-α and IL-1β levels.

Conclusion. The presence of CMV DNA and the level of CMV viral load are significant markers in predicting the development of cardiovascular events in patients with CHF within 24 months, which allows us to recommend their determination for early risk stratification of the unfavorable course of cardiac dysfunction.

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