NT-PROBNP LEVELS IN PATIENTS WITH COVID-19 AND HF

Full Text

Relevance: It is known that many viruses affect the heart, both as a result of direct viral processes and through indirect mechanisms associated with the body's immune response [1]. Analysis of the results of numerous studies leads to the conclusion that the absolute increase in the activity of viral diseases by 5 - 7% is directly related to an increase in the frequency of hospitalizations for heart failure by 24% or more.  Since the beginning of the pandemic, the number of coronavirus infections has reached 662,221,274, and the number of deaths has reached 6,701,780[2]. These figures are largely associated with the decompensation of heart failure as a result of the accession of respiratory infections and other intercurrent diseases.  Increased levels of cardiac biomarkers during coronavirus infection reflect excess inflammation, viral load, cytokine storm, and atherothrombotic process, which can cause direct or indirect heart damage [3].

Objective: To study nt-proBNP levels in patients with chronic heart failure who have had COVID-19.

Materials and methods: The study included patients aged 40 to 70 years with a diagnosis of CHF of ischemic genesis (including 33 men and 27 women, mean age 63.7±8.1 years) who underwent a full clinical and laboratory examination confirmed by a diagnosis of Covid-19, with a  positive polymerase chain reaction (PCR) smear from the nasopharynx for SARS-C oV infection -2 (n=60). The control group consisted of patients with symptoms and signs associated with Covid-19 and positive polymerase chain reaction (PCR) of a nasopharyngeal swab for SARS-C infection about V-2 patients, without symptoms and signs of HF in the anamnesis (n = 20).  All patients gave verbalvoluntary informed consent to participate in the study.  All clinical procedures and treatment were carried out in accordance with the current recommendations for the treatment of patients with a new coronavirus infection, as well as in accordance with the current recommendations of the Ministry of Health of Russia for the diagnosis and treatment of CHF (2020).

Clinical-instrumental and laboratory examination was performed on all patients included in the study: group 1 (60 patients with CHF and various LV EF during their hospitalization for novel coronavirus infection), group 2 (control group - 20 hospitalized with symptoms and signs associated with Covid-19 and positive polymerase chain reaction (PCR) nasopharyngeal swab for SARS-C infection about V -2 patients, without symptoms and signs of HF in the anamnesis).

The study did not include patients with chronic broncho-pulmonary diseases, chronic kidney disease (stage 3b and above), diabetes mellitus, persistent atrial fibrillation, anemia, diseases of the musculoskeletal system, obesity (2-3 degrees), oncological diseases, with an established diagnosis of chronic pulmonary heart.

All patients with CHF included in the study were observed by us since 2020, and during the entire period of observation of them after discharge from the hospital (hospitalization for  Covid-19), they had the opportunity to contact a cardiologist. Within six months, 8 people (6 people with CHF and 2 people with no history of symptoms and signs of HF) dropped out of the study due to the onset of death. . Laboratory methods were carried out: general clinical and enzyme-linked immunosorbent blood tests with determination of the level ofI NT-proBNP.

Statistical analysis was carried out using the Statistica 12 software package. The normality of the data distribution was assessed using a test (Shapira-Wilke). The initial continuous variables were presented as a standard mean deviation and compared using the Student t-criterion, in the form of a median and interquartile range, and compared using the Mann-Whitney and Kruskal-Wallis tests. Categorical ones were compared using the exact  the Fisher method. Differences between subgroups were considered statistically significant at a significance level of p<0.05.

Results: When comparing groups by biomarker levels, the following results were obtained. Mean NT-proBNP in patients with CHF (n = 60) (g. 1)  upon admission to the hospital amounted to 2640.89±1548.68 pg / ml (79; 6108), which significantly exceeded its value in patients without cVD in the anamnesis (gp.2) - 333.25±244.77 pg / ml (37; 812) (p<0.001).  Also, an analysis was carried out witha rare levelof I NT-proBNP in patients depending on FC (Fig.1): so the level  of the N-terminal fragmenta of the cerebral natriuretic peptide in patients with initial III FC CHF (subgr. 1. 3) amounted to 4008.53±1234.68 pg / ml (1930.0; 6108.0), which significantly exceeded its value in patients witho II FC CHF (subgr.1.2) - 2583.91±1214.23 pg / ml (87.0; 4470.0) (p<0.0001) and in patients with I FC CHF (subgr.1.1) amounted to 850.58 ±479.02 pg/ml (79.0; 1310).

The ratio of the odds of a favorable course  of CHF and Covid-19 or the transfer to the ICU of patients with CHF and Covid-19 depending on the level of Nt-proBNP (threshold value of ˃300 pg / ml) was studied.  The resulting OR was 12.27, [95% CI 1.53567; 98.1617]. Therefore, the probability of not getting into the ICU in patients with an NT-proBNP level  below the threshold is 12.27 times lower than in patients with an Nt-proBNP level  of ˃300 pg / ml.

Also, the ratio of chances of a favorable course of CHF and Covid-19 or death depending on the level of Nt-proBNP (threshold value of ˃300 pg / ml) was studied.  The resulting OR was 2.43 [95% CI 0.564593; 10.5233]. Therefore, the probability of non-occurrence of such a checkpoint as death in patients with an NT-proBNP level  below the threshold is 2.43 times lower than in patients with an Nt-proBNP level  of ˃300 pg / ml.

Discussion: It is known that the ventricular myocardium is responsible for the synthesis and secretion of NT-proBNP, and its effect is aimed at antifibrotic and natriuretic processes [4].  An increase in  NT-proBNP levels in CHF patients after covid-19 may indicate an  intensification of  the myocardial remodeling process. The data obtained in the study are consistent with the scientific hypothesis of an increase in NT-proBNP production in mechanically overloaded cardiomyocytes, reflecting myocardial stress, remodel ventricular ingress and fibrosis[5].  Based on the data obtained in the research, a potential role of a biomarker such  as Nt-proBNP in stratifying the risk of severe course / death in patients with SARS-CoV-2 infection is assumed.

Conclusion: The threshold values of the cardiac biomarkera (NT-proBNP) for stratification and isolation of risk groups among patients with Covid-19, CHF and Covid-19 have been determined. In patients with Covid-19 and CHF, a strong association has been found between high levels of the cardiac biomarker (Nt-proBNP) and a negative short-term prognosis.

About the authors

Yuliya O. Glavatskikh

Voronezh State Medical University named after N. N. Burdenko

Author for correspondence.
Email: Yuliyag36@gmail.com
ORCID iD: 0000-0002-2398-5987
SPIN-code: 9762-6156
Russian Federation, 10 Studentskaya str., Voronezh, 394036, Russia

Roman Е. Tokmachev

Voronezh State Medical University named after N. N. Burdenko

Email: r-tokmachev@mail.ru
ORCID iD: 0000-0001-6379-4635
SPIN-code: 5922-6679
10 Studentskaya str., Voronezh, 394036, Russia

Sofia А. Budnevskaya

Voronezh State Medical University named after N. N. Burdenko

Email: yuliyag36@gmail.com
ORCID iD: 0000-0003-3649-5642
10 Studentskaya str., Voronezh, 394036, Russia

Valeria R. Drobysheva

Voronezh State Medical University named after N. N. Burdenko

Email: drobyshevavr@gmail.com
ORCID iD: 0000-0001-6636-6644
10 Studentskaya str., Voronezh, 394036, Russia

References