The role of cytomegalovirus infection in ischemic heart failure progression
Authors: Grakova E , Shilov S.N , Berezikova E.N , Kopeva K.V , Popova A.A , Samsonova E.N , Pankova I.V , Teplyakov A.T 
Published: October 2021

Abstract

Objective
To study an association between cytomegalovirus infection (CMV) and molecular biomarkers (NT-proBNP, tumor necrosis factor (TNF-α), Interleukin-1β) and evaluate prognostic role of CMV infection in ischemic heart failure (HF) progression during the 12-month follow-up period.

Methods
A total of 104 patients (61.5% men, median age of 59 [53; 62.5] years) with stable coronary artery disease and baseline left ventricular ejection fraction (LVEF) of 43% [36; 57]% were enrolled in the study. At baseline evaluation HF patients were of New York Heart Association (NYHA) class I (7.7%), class II (61.0%), and class III (31.3%). Sixty five percent of patients had prior myocardial infarction and 70.2% received prior myocardial revascularization (coronary artery bypass graft/stent). Cytomegalovirus DNA concentrations in EDTA whole-blood samples were measured using a polymerase chain reaction baseline and at 12 months of follow-up period. Serum levels of NT-proBNP, Interleukin-1β, TNF-α were measured baseline using an enzyme immunoassay. Two-dimensional transthoracic echocardiography was performed at baseline and at the 12 months.

Results
At baseline, all patients were divided into 2 groups: group A comprised CMV seropositive patients (n=52); group B comprised CMV seronegative patients (n=52). Plasma concentration of cytomegalovirus DNA was 1709.4 [615; 3176] copies/mL. The values of cytomegalovirus DNA significantly correlated with NT-proBNP (r=0.781), TNF-α (r=0.799) and Interleukin-1β (r=0.756). Levels of NT-proBNP were higher (p=0.0001) in group A by 36.6% than in group 2 (559 [364; 756] vs. 354.5 [279; 545.5] pg/mL, respectively). Levels of TNF-α were also higher (p&lt;0,001) by 35.3% (8.5 [6.5; 10.9] vs. 5.5 [4.1; 7.3] ng/mL, respectively) and levels of Interleukin-1β (p&lt;0,001) by 17.6% (19.3 [15.8; 23.75] vs. 15.9 [13.15; 18.7] ng/mL, respectively) in group A than in group B. During the 12-month follow-up period in group A the rate of HF progression was 51.6% cases, and in group B 26.9% (p=0.009). Based on ROC-analysis, baseline plasma concentration of cytomegalovirus DNA ≥2020 copies/mL (AUC=0.798; specificity 67%, sensitivity 82%; p&lt;0.001) were identified as a cut-off values predicting development of HF progression during the 12-month follow-up period. 12-month levels of cytomegalovirus DNA did not differ (p=0,678) in comparison to baseline ones and were 1737.9 [321; 3384] copies /mL. In group A LVEF significantly increased by 18.8% from 50.5 [36.5; 56.0] to 41.0 [35.0; 50.0]%, end-systolic dimension significantly increased by 7.3%, end-diastolic dimension by 9.6% (p&lt;0,0001), while in group B these parameters did not change.

Conclusion
Our data suggest that values of cytomegalovirus DNA are associated with NT-proBNP, TNF-α, Interleukin-1β levels, and may be considered as non-invasive biomarker for prediction of ischemic heart failure progression during the 12-month follow-up period.

Funding Acknowledgement
Type of funding sources: None.