NT Pro‐BNP can be used as a risk predictor of clinical atrial fibrillation with or without left atrial enlargement

Abstract Background NT Pro‐BNP is a blood marker secreted by cardiomyocytes. Myocardial stretch is the main factor to stimulate NT Pro‐BNP secretion in cardiomyocytes. NT Pro‐BNP is an important risk factor for cardiac dysfunction, stroke, and pulmonary embolism. So does atrial myocyte stretching occur when patients have atrial fibrillation (AF)? Whether atrial muscle stretch induced by AF leads to increased NT Pro‐BNP remains unclear. The purpose of this study is to investigate the relationship between NT Pro‐BNP and AF. Hypothesis AF can cause changes in myocardial tension. Changes in myocardial tension may lead to increased secretion of NT Pro‐BNP. We hypothesize that NT Pro‐BNP may increase in AF with or without LAD enlargement. Methods This clinical study is an observational study and has been approved by the Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University. Ethical approval documents is attached. The study retrospectively reviewed 1345 patients with and without AF. After excluding 102 patients who were not eligible, the final total sample size was 1243 cases: AF group 679 patients (378, 55.7% males) and non‐AF group 564 patients (287, 50.8% males). NT Pro‐BNP was observed in AF group and non‐AF group with or without LAD. After adjusting for age, gender, BMI, left atrial diameter, hypertension, diabetes, coronary heart disease, and cerebral infarction, NT Pro‐BNP remains statistically significant with AF. Conclusion NT Pro‐BNP can be used as a risk predictor of AF with or without left atrial enlargement.

AF. The purpose of this experiment was to explore whether AF can cause changes in NT Pro-BNP secretion and whether NT Pro-BNP can be considered as a risk factor for the occurrence of AF.
2 | METHOD 2.1 | The experimental flow chart of AF and non-AF patients Figure 1 shows the entire process of the experiment.

| Inclusion criteria for patients with AF
• More than two episodes of AF occurred and recorded by ECG before.
• Aged from 18 to 80 years old.

| Exclusion criteria for patients
Valvular Heart disease, cardiomyopathy, hyperthyroidism, anemia, congenital heart disease, and severe cardiac dysfunction (EF < 35%) were excluded. The normal range of NT Pro-BNP is 0-125 pg/ml, once it is above 125 pg/ml, we define it as the increase of NT Pro-BNP.

| Case selection
This experiment aims to explore the role of NT Pro-BNP in AF patients. A total of 1243 patients were enrolled from the Atrial Fibrillation Center, Department of Cardiology, the First Affiliated Hospital of Xi'an Jiaotong University. According to the inclusion and exclusion criteria, 679 patients with AF and 546 patients without AF were included. We also conducted subgroup analysis on the AF group and non-AF group, we divided them into the NT Pro-BNP increase group and the NT Pro-BNP normal group separately according to the criterion of NT Pro-BNP increased. When we are exploring the relationship between NT Pro-BNP and AF, the influence of left ventricular diastolic diameter and left atrial diastolic diameter must be excluded. The relationship between NT Pro-BNP and AF were observed when the diameter of the heart was within the normal range.

| Statistical analysis
We used two independent sample t-tests for continuous data and χ 2 tests for discontinuous data.    As it is shown in    In conclusion, when AF was compared with the non-AF group, AF was associated with an increase in NT Pro-BNP regardless of the presence of left atrial enlargement.

| DISCUSSION
AF is one of the most common arrhythmias in clinical practice 3 and a major source for cardiovascular and cerebrovascular morbidity and mortality. 4 AF is also associated with higher rates of stroke and hospitalization, 5,6 decreased quality of life, 7 increased risk of heart failure and with the increase of mortality. Moreover, AF is considered to account for nearly half of all embolic strokes. 8 Identifying risk factors for AF is an important task for public health. 9,10 The supplement the risk factors of AF is conducive to early identification, early intervention and early treatment for AF to prevent the occurrence of stroke and embolism. Biomarkers in the blood are potential tools for predicting AF risk and providing insights into the pathophysiology of the disease. NT Pro-BNP may provide a better diagnostic resolution. 14,15 In the past, BNP has emerged as a powerful diagnostic tool for detecting acute heart failure and left ventricle systolic and/or diastolic dysfunction. 20,21 High BNP level is associated with left atrial auricle thrombosis, 22 and may also be a predictor of thromboembolism in patients with pulmonary embolism. Patients with normal NT Pro-BNP levels have a lower risk of death and hemodynamic deterioration leading to any adverse events. 19 However, with the development of research in recent years, it has been reported that the NT Pro-BNP is also produced in the atrial wall, 17 the main stimulus for cardiac NT Pro-BNP secretion is myocardial stretch; 16 AF is usually associated with changes in atrial muscle tone and may also lead to changes in NT Pro-BNP secretion. found that the level of NT Pro-BNP in the left atrial normal group in AF was also statistically higher than that in the non-AF group (p < .001).
Through the above research results we found that even without obvious left atrial enlargement of AF, minor, irregular and asynchronous atrial myocardial stretch during AF may still lead to changes in myocardial stretch, which may also lead to the increase of NT Pro-BNP.
The results of this experiment showed that: regardless of the presence or absence of enlarged left atrium, the NT Pro-BNP in the AF group was significantly higher than that of the non-AF group. NT Pro-BNP can be a risk factor for the occurrence of AF, no matter with or without the influence of enlarged left atrium.

| CONCLUSION
NT Pro-BNP can be used as a risk predictor of AF with or without left atrial enlargement.

| LIMITATION
As an observational study, this study has limitations, including the data is obtained from a single center, the data is not representative enough, the sample size of the data needs to be expanded, and some Note: Data shows an analysis of left atrial enlargement subgroups in the AF and non-AF groups.
ZHAO ET AL.
| 73 data are missing. However, the whole 1243 cases were all obtained from the our hospital after ethical approval, which could represent our team's overall interests.