The Relation Between Global Longitudinal Strain and Serum Natriuretic Peptide Is More Strict Than That Found Between the Latter and Left Ventricular Ejection Fraction: A Retrospective Study in Chronic Heart Failure

Abstract

Background: In chronic heart failure (CHF), the finding of elevated levels of the N-terminal fragment of the pro B-type natriuretic peptide (NT-proBNP) is a marker of pathological increase in myocardial ventricular wall stress and detrimental rise in ventricular filling pressures. However, the ensemble of data concerning the relationship between longitudinal deformation indices and NT-proBNP is still rather vague and approximate.

Methods: We carried out a retrospective study that involved 118 patients with CHF admitted to our clinic for CHF outpatients. For inclusion in the study, the CHF patients were required to have undergone at least a determination of global longitudinal strain (GLS) by means of speckle tracking echocardiography and to have practiced at least a determination of NT-proBNP. As regards the two determinations, the one echocardiographic and the other laboratory-based, the former should have been done not more than 24 hours before or after the latter.

Results: Correlation between log (NT-proBNP) and GLS was highly significant (r = 0.8386; P < 0.0001). The observed correlation between log (NT-proBNP) and left ventricular ejection fraction (LVEF) was also significant, but explained a smaller magnitude of the variance (r = -0.5465; P < 0.0001). In multiple linear regression analysis, GLS was shown to be the strongest independent predictor of log (NT-proBNP), within a parsimonious model including age, body mass index, estimated glomerular filtration rate, left atrial volume index, and LVEF (β (regression coefficient) = 305, rpartial = 0.7076; P < 0.0001). By using the median value of NT-proBNP (299.5 pg/mL) as a discriminating value for identifying relatively low (i.e., below the median) and relatively high (i.e., above the median) levels of NT-proBNP, GLS was associated with the upper quartiles, whereas LVEF was associated with lower quartiles of NT-proBNP. However, the C statistics for GLS were significantly higher than for LVEF (area under the curve (AUC): 0.949 (GLS) vs. 0.730 (LVEF); P = 0.0030).

Conclusions: In CHF patients, GLS shows a stronger association with NT-proBNP levels with respect to LVEF. Thus, in both CHF with preserved and reduced LVEF, GLS is more accurate compared with LVEF in predicting increased levels of NT-proBNP.

Keywords: Chronic heart failure; Global longitudinal strain; Left ventricular ejection fraction; Natriuretic peptides; Speckle tracking.

Figure 1

The values of GLS (%) of each patient are plotted against the respective values of serum NT-proBNP. Each circlet, corresponding to a given value of GLS, falls in one of the four groups of circlets coincident with the quartiles of NT-proBNP derived from the categorization of the entire range of possible NT-proBNP values in the context of the 50 patients included in the study. The lowest quartile includes the NT-proBNP values ≤ 58 pg/mL, the quartile between the 26th percentile and the median (50th percentile) includes values > 58 and ≤ 299.5 pg/mL, the quartile between 51th and the 75th percentile includes the values > 299.5 and ≤ 1,405 pg/mL, the highest quartile incorporates the values > 1,405 pg/mL up to the highest value found, i.e., 4,123 pg/mL. Note that the less pronounced cases of global longitudinal systolic deformation are grouped in the highest quartile of the distribution of the values of NT-proBNP, while the most efficient cases of GLS (characterized by the most negative values) are grouped in the lowest quartile of NT-proBNP. Please note also that the increasing (i.e., progressively less negative) values of GLS are coupled with progressively increasing values of NT-proBNP, according to a direct linear relationship (Fig. 2). GLS: global longitudinal strain; NT-proBNP: N-terminal fragment of the prohormone of the B-type natriuretic peptide.

Figure 2

Linear regression model derived from the patient population of the present study. The model includes the B-type natriuretic peptide (log NT-proBNP), which is the dependent variable y, on the vertical axis, and the global longitudinal strain (GLS) on the horizontal axis. As the global longitudinal systolic deformation of the left ventricular chamber is reduced, the value of the NT-proBNP, a marker of myocardial left ventricular intracavitary tension, progressively increases. In other words, those who have the less negative values of global systolic longitudinal strain, that is, who have weaker systolic shortening of the left ventricular chamber due to less valid longitudinal contraction of the subendocardial fibers, are also those having the highest circulating levels of B-type natriuretic peptide. More impaired is the longitudinal contractile function, the higher the value of the serum natriuretic peptide. GLS: global longitudinal strain; NT-proBNP: N-terminal fragment of the pro B-type natriuretic peptide; pg: picograms; log: logarithmic transformation of Y.

Figure 3

The values of LVEF (%) of each patient are plotted against the respective values of serum NT-proBNP. Each circlet, corresponding to a given value of LVEF, falls in one of the four groups of circlets coincident with the quartiles of NT-proBNP derived from the categorization of the entire range of possible NT-proBNP values in the context of the 50 patients included in the study. The lowest quartile includes the NT-proBNP values ≤ 58 pg/mL, the quartile between the 26th percentile and the median (50th percentile) includes values > 58 and ≤ 299.5 pg/mL, the quartile between 51th and the 75th percentile includes the values > 299.5 and ≤ 1,405 pg/mL, the highest quartile incorporates the values > 1,405 pg/mL up to the highest value found, i.e., 4,123 pg/mL. Please note that the values of LVEF are distributed within the whole range of the possible NT-proBNP values, so it is not possible to identify the existence of a significant inverse linear relationship between LVEF and serum NT-proBNP in the study population (Fig. 4). LVEF: left ventricular ejection fraction; NT-proBNP: N-terminal fragment of the prohormone of the B-type natriuretic peptide.

Figure 4

Linear regression model derived from the patient population of the present study. The model includes the NT-proBNP that undergoes logarithmic transformation (log NT-proBNP), assumed as the dependent variable y and placed on the vertical axis, and the left ventricular ejection fraction (LVEF), put on the horizontal axis. As the LVEF progressively decreases across the whole range of the possible values that it can assume within the entire patient population, the value of the NT-proBNP, a marker of myocardial left ventricular intracavitary tension, progressively increases. However, the strength of the relationship is much less marked (r = -0.5465) with respect to that characterizing the relation between log NT-proBNP and GLS (r = 0.8386; Fig. 2). NT-proBNP: N-terminal fragment of the pro B-type natriuretic peptide; pg: picograms; LVEF: left ventricular ejection fraction; log: logarithmic transformation of Y; GLS: global longitudinal strain.

Figure 5

In this ROC plot, there is the representation of the diagnostic performance (AUC = 0.949) of GLS as a predictor of relatively high values (> 299.5 pg/mL) of NT-proBNP among 50 CHF patients. GLS: global longitudinal strain; ROC: receiver operating characteristic; NT-proBNP: N-terminal fragment of the pro B-type natriuretic peptide; pg: pictograms.

Figure 6

In this ROC plot, there is the representation of the diagnostic performance (AUC = 0.730) of the LVEF as a predictor of relatively high values (> 299.5 pg/mL) of NT-proBNP among 50 CHF patients. LVEF: left ventricular ejection fraction; ROC: receiver operating characteristic; NT-proBNP: N-terminal fragment of the pro B-type natriuretic peptide; pg: picograms.

Figure 7

In this ROC plot, the area under the curve (AUC) that characterizes GLS for detection of an NT-proBNP > 299.5 pg/mL (classification variable) is compared with the corresponding AUC exhibited by LVEF within the study population. GLS: global longitudinal strain; LVEF: left ventricular ejection fraction; SE: standard error; CI: confidence interval.