The study aimed to evaluate the relationship between NT-proBNP levels and left ventricular diastolic dysfunction in patients with COVID-19. Our study showed that plasma NT-proBNP levels in patients with increased diastolic dysfunction was related to the severity of the disease so that with increasing severity of diastolic dysfunction, proBNP levels also increase. It was also found that the cut-off point of NT-proBNP = 799 pg/mL could be used as a predictor of diastolic dysfunction grades 2 and 3. A person with COVID-19 who has high-grade diastolic dysfunction is 100% likely to have a serum proBNP level above 799 pg/mL. In this study, patients with a serum proBNP level above 799 had a 37 times higher chance of having diastolic dysfunction than those with a serum proBNP level below this amount. There are studies that, like our study, found significantly higher proBNP levels in patients with advanced diastolic dysfunction.
In one study this level was 286 ± 31 pg/mL (13), in another study the proBNP level was 46 to 48 pg/mL above normal (14) and in another study, it was 14 ± 13 pmol/l (15). Although these late peptides have been shown to be associated with severe diastolic dysfunction, their role in the diagnosis of mild diastolic heart failure is uncertain (16). In a study on 396 patients that showed a strong association between plasma NT-proBNP levels and the risk of death in COVID-19 patients, the best median NT-proBNP for predicting mortality at 53 days of follow-up was 847.5 pg/ml. According to this study, NT-proBNP was associated with mortality both in the entire study population and after the exclusion of HF patients. NT-proBNP above this level was associated with a higher risk of mortality in these patients due to cardiac complications raised by complex interactions between previous conditions, ischemia, systemic inflammation, and direct pathogen damage to the cardiovascular system (17). This amount was lower than the cut-off of our study which predicted grade 2 and 3 diastolic dysfunctions as a poor outcome.
According to an article published in the European Heart Association in 2016, a cut-off point of 125, along with other anatomical and functional signs, was used to diagnose diastolic heart failure. In COVID-19 patients, Pro-BNP levels cannot be satisfied with the previous standard figures due to the possibility of high levels of infection, inflammation and hypoxia. It seems that a different cut-off point should be considered. Based on the results of this study, NT-proBNP levels above 799 pg/ml were obtained to diagnose high-grade diastolic dysfunction in patients with severe COVID-19 (18). The sensitivity of NT-proBNP for the diagnosis of diastolic dysfunction in our study was 100% and it was an accurate screening test that in Lu Bien study (13) had a sensitivity of 85% for the diagnosis of diastolic dysfunction in non-COVID patients, this value in another study was reported to be 69% and NT-proBNP was not recommended for screening diastolic dysfunction. However, this study was performed on people over 45 living in the community years before the COVID pandemic who were randomly included in the study (19).
In this study, we compared NT-proBNP for the diagnosis of diastolic dysfunction in hospitalized patients with COVID-19 with echocardiographic indices as a routine non-invasive procedure. However, the standard for assessing diastolic heart function is to measure the pressure-volume relationship with a catheter, which is an invasive procedure. In our study, there was a positive correlation between proBNP levels and some echocardiographic parameters including RA_size, LVED, LV_ Ee, and LV_E, and this indicates that as proBNP levels increase, these indices also increase. Significant negative correlation between proBNP level and one of the echocardiographic parameters including LVEF increases with decreasing LVEF serum NT-proBNP level number. According to this study, proBNP above 556 pg/ml in severe COVID-19 patients has a predictive value of 97.2% for the presence of RV_EA > 2 and also proBNP above 556 pg/ml in these patients has a predictive value of 63.9% for the presence of LV_Ee > 4 in echocardiography. These two echocardiographic parameters indicate an increase in right heart filling pressures and due to the relationship between right heart pressure and left heart filling pressures and its relationship with pulmonary pressure, hypoxia and lung pressures, it seems that diastolic dysfunction of the right side of the heart begins at lower levels of proBNP.
According to other results from this study, if a person has a proBNP above 1479 pg/ml, LV_E would be greater than 50 cm for 100% (E wave velocity above 50). Given that the E-wave velocity showed a compression gradient between the atrium and the ventricle and depend on left ventricular complication and left ventricular pressure, it could be said that proBNP above 1479 pg/ml should avoid volumetric and compressive overload. In this study, for every unit increase in SPAP, the chance of diastolic dysfunction increased by 22%. SPAP levels are associated with inflammation and hypoxia of the lungs and are also associated with increased and limited left-filling pressures. The limitations of this study included it was an observational, single-center study with the inherent limitations of this type of design. The number of samples and the possibility of performing echocardiography were limited due to policies focused on prevention of SARS-CoV-2 transmission.