The Value Of Plasma NT-proBNP In The Diagnosis Of Diastolic Heart Failure In Hypertensive Patients

BackgroundDiastolic heart failure (DHF) occurs in 30%-50% of patients presenting with congestive heart failure (CHF), and is associated with a poor prognosis. However, with few clinical trials taken on it, there are still no generally accepted diagnostic criteria or management guideline of DHF, mainly because it is difficult to evaluate diastolic function. The sensitivity and specificity of Doppler echocardiography in detecting diastolic dysfunction are unsatisfactory due to many factors. Though more reliable, the invasive cardiac catheterization is not widely used in clinical practice. Thus, objective, sensitive, specific, simple and non-invasive diagnostic parameter of DHF would be of high clinical value. N-terminal pro-BNP (NT-proBNP) is important cardiac neurohormone hallmarks secreted from the ventricules in response to ventricular volume expansion and pressure overload. Previous studies have reported that NT-proBNP have important value in diagnosing, grading the severity and evaluating the prognosis of systolic heart failure (SHF), but the value of NT-proBNP in the diagnosis of DHF is still under investigation.ObjectiveThis study was to investigate the relations of plasma NT-proBNP to clinical DHF severity, plasma NT-proBNP to diastolic dysfunction degree and plasma NT-proBNP to echocardiography indices about diastolic function, and to get a cut-off value of plasma NT-proBNP in diagnosing DHF in hypertensive patients. Methods61 hypertensive in-patients and out-patients without SHF were selected for the study. Patients without CHF or diastolic dysfunction were classified as group I, patients without CHF but with diastolic dysfunction were classified as group II and patients with both CHF and diastolic dysfunction were classified as group III. 20 healthy people were selected as control group. Heart function was classified as NYHA I to IVaccording to clinical data. Diastolic function, measured in 24 hours after admission or visit by Doppler echocardiographic, was classified as normal, impaired relaxation, pseudonormal, and restrictivelike filling patterns. Plasma NT-proBNP was measured in 24 hours after admission or visit. Then plasma level of NT-proBNP was compared respectively within study groups, diastolic function grades and NYHA classifications. The relations of echocardiographic indices to diastolic function, echocardiographic indices to NT-proBNP, and LVMI to NT-proBNP were evaluated. ROC curves were constructed to determine the ability and optimal cut-off points of NT-proBNP for identifying diastolic dysfunction and diastolic heart failure.Results1. NT-proBNP levels increased with the occurrence of diastolic dysfunction and CHF, from 40.35 (5.0-86.0) pg/ml in control group to 95.27 (29.0-256.0) pg/ml in group I , 184.00 (95.9-302.3) pg/ml in group II and 684.07 (103.3-5692.0) pg/ml in group III, with significant difference between any two groups (P<0.05).2. NT-proBNP levels increased significantly according to the severity of diastolic dysfunction, from 59.84 (5.0-256.0) pg/ml in grade I to 195.35 (95.9-482.8) pg/ml in grade II, 519.43 (275.2-1173.0) pg/ml in grade IIIand 2963.80 (1396.0-5692.0) pg/ml in grade IV, with significant difference between any two grades (P<0.01), and correlated with the Pearson coefficient r=0.812 (P<0.001).3.NT-proBNP levels increased significantly according to the NYHA-classification, each group being higher than the control group, from 40.35 (5.0-86.0) pg/ml in control group, to 147.85 (29.0-302.3) pg/ml in NYHA I, 266.16 (103.3-1173.0) pg/ml in NYHAII, 1116.54 (136.6-3965.0) pg/ml in NYHAIII and 3544.00 (1396.0-5692.0) pg/ml in NYHAIV, with significant difference between any two classifications (P<0.05), and correlated with r=0.741 (P<0.001).4. Within diastolic function grade II to IV, Doppler echocardiographic indices E/A increased, DT and IVRT decreased according to the severity of diastolic dysfunction(P<0.05). But E/A, DT and IVRT were not significantly different between grade IH(pseudonormal) and grade I (normal). Ea, Ea/Aa and Vp in grade I were respectively higher than in grade II to IV. But there were no significant difference of Ea, Ea/Aa and Vp within grade II to IV. Diastolic function correlated with E/A(r=0.446, P<0.001), Ea(r=-0.615, P<0.001), Ea/Aa(r=-0.674, P<0.001) and Vp(r= -0.572, P<0.001), but did not correlate significantly with DT, IVRT or LVMI.5. NT-proBNP correlated with Doppler echocardiographic indices E/A(r=0.315, P=0.004), Ea(r=-0.589, P<0.001), Ea/Aa(r=-0.228, P=0.041) and Vp(r=-0.583, P<0.001), but did not correlate significantly with DT or IVRT.6. NT-proBNP level of patients with left ventricular hypertrophy was 392.27 (27.0-5692.0) pg/ml, higher than that of patients with normal LVMI, the latter was 289.04 (5.0-3965.0) pg/ml, P<0.01. NT-proBNP positively correlated with LVMI (r=0.341,P=0.002).7. The ROC curve of NT-proBNP defining diastolic dysfunction had an AUC of 0.972 (95%CI 0.930-1.013, P<0.001). Using a cut-off value of 99.65pg/ml, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of NT-proBNP defining diastolic dysfunction were 98.0%, 90.3%, 94.1% and 93.3%, respectively.8. The ROC curve of NT-proBNP diagnosing DHF had an AUC of 0.886 (95%CI 0.818-0.954, P<0.001). Using a cut-off value of 112.45pg/ml, the sensitivity, specificity, PPV and NPV of NT-proBNP diagnosing DHF were 94.0%, 81.8%, 72.7% and 94.6%, respectively.Conclusions1. NT-proBNP can reliably diagnose diastolic heart failure in hypertensive patients. High sensitivity and NPV make NT-proBNP have great clinical value in screening diastolic dysfunction in high-risk group and ruling out diastolic heart failure.2. NT-proBNP can assess the severity of diastolic heart failure in hypertensive patients, having good correlation with diastolic dysfunction grades and NYHA classifications.3. Diagnostic value of NT-proBNP to diastolic heart failure in hypertensive patients is independent of left ventricular hypertrophy.4. NT-proBNP has good correlation with several Doppler echocardiographic indices, which makes it possible to analyze NT-proBNP in association with echocardiographic indices to improve diagnostic accuracy of diastolic heart failure in hypertensive patients.