A novel global strain diastolic index correlates with plasma NT-proBNP levels in asymptomatic hypertensive patients with preserved left ventricular ejection fraction
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- Chiang, SJ., Daimon, M., Ishii, K. et al. J Echocardiogr (2012) 10: 56. doi:10.1007/s12574-012-0122-4
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The strain imaging diastolic index (SI-DI) was reported to be a sensitive marker of regional left ventricular (LV) delayed relaxation induced by ischemia. However, the clinical usefulness of the global SI-DI has not been evaluated. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a sensitive biomarker for the detection of asymptomatic diastolic LV dysfunction. This study investigated the ability of a novel parameter, the global SI-DI, obtained using 2D speckle tracking imaging (2DSI) to correlate with the plasma NT-proBNP levels in asymptomatic hypertensive patients with preserved LV ejection fraction.
We performed 2D echocardiography and 2DSI in 83 asymptomatic hypertensive patients with preserved ejection fraction (>45 %) and in 37 control subjects. In 2DSI, the LV longitudinal peak strain and the SI-DI of 18 LV segments were measured. NT-proBNP was measured in all subjects. The data were compared between hypertensive patients and normal controls.
The average peak strain and global SI-DI of 18 LV segments were significantly reduced in hypertensive patients compared with control subjects (P < 0.05); however, only the global SI-DI was significantly correlated with log10 NT-proBNP (r = −0.469, P = 0.001). In Pearson’s correlation analyses, log10 NT-proBNP was significantly correlated with E/e′, E/A ratio, early diastolic mitral annular velocity (e′), global peak strain, deceleration time of the E-wave, and LV ejection fraction. In the multiple stepwise regression analysis, the global SI-DI was the strongest independent determinant of log10 NT-proBNP (β = −0.386, P = 0.008).
The global SI-DI derived from 2DSI correlates well with plasma NT-proBNP levels and may have prognostic value in asymptomatic hypertensive patients with preserved ejection fraction.
KeywordsHypertension Echocardiography Brain natriuretic peptides Ultrasonic diagnosis
Hypertension is the most common risk factor associated with heart failure (HF) in the general population . In the process of left ventricular (LV) remodeling, changes in LV diastolic characteristics occur that precede changes in LV systolic function. In fact, more than half of the patients with HF present with normal ejection fraction and diastolic dysfunction . Thus, it is important to identify asymptomatic hypertensive patients who are at risk of developing diastolic HF among those with normal LV systolic function. Strain imaging derived from 2D speckle tracking echocardiography enables the quantification of regional wall motion without tethering effect and Doppler angle dependency [3, 4, 5]. A number of previous investigations have emphasized the clinical value of systolic strain imaging in assessing myocardial systolic dysfunction in patients with HF [6, 7, 8, 9, 10, 11]. Although some investigations have assessed diastolic function with strain imaging, the clinical value of diastolic strain has not yet been firmly established [12, 13, 14].
Recently, the strain imaging diastolic index (SI-DI) was reported to be a sensitive marker to detect regional LV delayed relaxation during early diastole induced by myocardial ischemia [15, 16]. However, no previous studies have examined the clinical usefulness of the global SI-DI. We hypothesized that a novel parameter, the global SI-DI, may be useful in identifying asymptomatic hypertensive patients with a preserved ejection fraction who are at high risk of developing diastolic HF. Therefore, we examined the value of the global SI-DI for assessing latent LV diastolic dysfunction in asymptomatic hypertensive patients with preserved ejection fraction. Since plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) is a powerful neurohumoral prognostic factor in HF with preserved ejection fraction [17, 18, 19], we also determined the ability of the global SI-DI to correlate with plasma NT-proBNP levels.
Materials and methods
The study included 83 consecutive asymptomatic patients with essential hypertension from an outpatient clinic population. All patients fulfilled the following criteria: (1) a past history of systolic blood pressure (BP) ≥140 mmHg and/or diastolic BP ≥90 mmHg in two or more hospital visits at 2-week intervals without antihypertensive medication; (2) continued hypertensive treatment for ≤12 months; (3) no clinical, laboratory, or echocardiographic evidence of congestive HF, regional LV wall motion abnormalities, significant valvular heart disease, coronary artery disease, secondary causes of hypertension, diabetes mellitus, chronic renal failure, or other important concomitant disease; (4) LV ejection fraction ≥45 %; and (5) good-quality echocardiographic images. Any subjects who had atrial or ventricular arrhythmias, pacemaker implantation, bundle branch block, significant valvular heart disease, or a past history of coronary artery disease or congestive HF were excluded from the study. We also excluded subjects with poor and inadequate images for strain analysis. A total of 37 age-matched subjects without a history of cardiovascular disease served as the control group. The control subjects also had normal clinical and laboratory findings, and no abnormal findings on conventional echocardiography or exercise stress testing. The study protocol was approved by the Institutional Review Board of Juntendo University Hospital and Taipei City Hospital.
Analysis of the strain diastolic index
Conventional 2D and Doppler echocardiography
Conventional echocardiographic measurements were also performed in all subjects. The LV diameter was measured at both end systole and end diastole by M-mode echocardiography. The thickness of the interventricular septum and the LV posterior wall were measured at end systole. These parameters were used in a previously reported equation to calculate the LV mass . The LV end-diastolic volume and end-systolic volume were determined from biplane images using a modification of Simpson’s method. The ejection fraction (%) was calculated by the following equation: 100 × (end-diastolic volume − end-systolic volume)/end-diastolic volume. The left atrial volume was measured using the biplane area–length method. Each parameter obtained from the chamber quantification was indexed for the body surface area (BSA), when appropriate.
For assessing conventional diastolic parameters, mitral inflow and tissue Doppler imaging were also examined . The peak early diastolic velocity (E), the deceleration time from the peak of the early diastolic wave to baseline (E-Dec time), the peak atrial systolic velocity (A), and the E/A ratio were assessed. The mitral annular motion velocity was recorded at the medial mitral annulus site in the apical 4-chamber view by pulsed tissue Doppler echocardiography. The peak early diastolic motion velocity (e′), peak motion velocity during atrial systole (a′), and the ratio of the peak early diastolic transmitral flow velocity E to e′ (E/e′) were calculated .
Blood test for NT-proBNP
Blood samples for the measurement of NT-proBNP were drawn in all hypertensive patients and normal controls at rest on the same day as echocardiography. Plasma NT-proBNP levels were determined using a commercially available sandwich immunoassay (Elecsys™) and an automated bench-top analyzer (Elecsys 2010, Roche Diagnostics, Germany). All echocardiographic measurements were obtained without knowledge of the NT-proBNP data.
Values are expressed as the mean ± standard deviation. Comparison of variables between the hypertensive and control groups was performed using an unpaired t test or one-way analysis of variance (ANOVA) with Tukey’s post hoc test. When the data were not normally disturbed, a Kruskal–Wallis test was performed. Categorical data were compared between the two groups with a Chi-squared test. Pearson’s linear correlation analysis was used to determine the correlations between log10 NT-proBNP and the echocardiographic variables. Multiple linear regression analysis was also performed to determine the independent determinants of log10 NT-proBNP among the echocardiographic parameters. All statistical analyses were performed with SPSS software version 17.0 (SPSS Inc., Chicago, IL, USA). A P value less than 0.05 was considered to be statistically significant for all analyses.
Patient characteristics and conventional echocardiography
Characteristics of hypertensive patients and normal control subjects
Control (n = 37)
Hypertension (n = 83)
52.9 ± 17.8
57.5 ± 11.5
164.8 ± 7.5
163.5 ± 7.5
59.4 ± 9.0
65.1 ± 10.5
21.8 ± 2.5
24.3 ± 3.0
1.7 ± 0.2
1.7 ± 0.2
0.8 ± 0.5
0.9 ± 0.7
Heart rate (beats per minute)
72.8 ± 6.7
73.8 ± 9.8
Systolic blood pressure (mmHg)
118.9 ± 10.3
133.5 ± 7.6
Diastolic blood pressure (mmHg)
67.2 ± 7.1
77.8 ± 7.9
ARB + diuretic
Results of the conventional echocardiography
Control (n = 37)
Hypertension (n = 83)
IVS thickness (cm)
0.9 ± 0.1
1.1 ± 0.1
PW thickness (cm)
0.9 ± 0.1
1.1 ± 0.1
4.4 ± 0.5
4.4 ± 0.5
2.9 ± 0.4
2.7 ± 0.5
LAV index (ml/m2)
17.4 ± 3.4
19.5 ± 4.7
LV mass index (g/m2)
81.4 ± 11.0
90.6 ± 24.1
Ejection fraction (%)
59.3 ± 8.4
56.5 ± 7.3
75.8 ± 17.3
65.9 ± 15.4
61.2 ± 18.1
75.2 ± 17.7
1.4 ± 0.6
0.9 ± 0.3
E-Dec time (ms)
187.2 ± 35.6
224.2 ± 44.1
7.9 ± 1.9
9.3 ± 2.5
10.0 ± 2.5
7.5 ± 1.9
SI-DI and peak strain
The peak strain was also reduced in every segment in the 4-, 3-, and 2-chamber views in hypertensive patients compared with the controls. Thus, the global peak strain was significantly lower in the hypertensive group than in the control group (−17.9 ± 3.3 vs. −20.8 ± 4.5, respectively, P < 0.001).
Global SI-DI, echocardiographic parameters, and log10 NT-proBNP
The effect of echocardiographic parameters on log 10 N-terminal pro-brain natriuretic peptide (NT-proBNP)
LV mass index (g/m2)
LAV index (ml/m2)
Ejection fraction (%)
Global peak strain
Deceleration time of the E-wave
In the current study, we demonstrated the usefulness of a novel parameter, the global SI-DI, to find the correlation with the plasma NT-proBNP levels in asymptomatic hypertensive patients with preserved ejection fraction. Presumably, these asymptomatic patients with elevated NT-proBNP are at increased risk of developing diastolic HF in the future. Furthermore, the global SI-DI was a more sensitive marker for predicting elevated NT-proBNP than conventional diastolic parameters obtained from mitral inflow and tissue Doppler imaging, which have been recognized as standard prognostic indicators in diastolic HF. Our results indicate that the global SI-DI might serve as a novel echocardiographic parameter for assessing diastolic function.
In patients with hypertension, the deterioration of diastolic function precedes the impairment of systolic function and plays a major role in the pathophysiology of HF. Thus, it is clinically important to detect the deterioration of diastolic function accurately at an early stage of HF. The SI-DI has been proposed as a sensitive marker to detect regional LV delayed relaxation induced by myocardial ischemia [15, 16]. Furthermore, LV delayed relaxation is a characteristic of early-stage diastolic dysfunction that might lead to restrictive physiology . In addition, recent studies showed that the reproducibility of global strain parameters was better than that of regional strain parameters . Thus, we presume that the global SI-DI might be useful in assessing diastolic function at an early stage in asymptomatic patients with latent LV dysfunction.
Although several studies have established the clinical value of systolic strain, there is much less information on diastolic strain. In the current study, we examined the clinical value of diastolic strain in asymptomatic patients who had not yet developed HF, whereas previous studies evaluated diastolic strain in patients with overt HF [13, 14]. NT-proBNP was significantly elevated even in our asymptomatic hypertensive patients compared with normal controls. NT-proBNP is a powerful prognostic factor [17, 18, 19] that is strongly correlated with the LV filling pressure, as determined by invasive methods . Thus, we assume that the global SI-DI might predict the risk of the development of HF with elevated filling pressure in asymptomatic hypertensive patients.
Interestingly, both the global peak strain and the global SI-DI were reduced in hypertensive patients compared with normal control subjects. However, the presence of hypertension did not appear to alter the LV ejection fraction. Some investigations [7, 11] reported decreased systolic function assessed by 2D speckle tracking in patients with preserved ejection fraction. These results indicate that LV contraction assessed by 2D speckle tracking may be superior to the conventional LV ejection fraction for evaluating LV systolic dysfunction. Despite the reduction in global strain in hypertensive patients with preserved ejection fraction in the present study, only the SI-DI was a major independent determinant of NT-proBNP. This finding emphasizes the importance of assessing diastolic function in patients with normal ejection fraction, regardless of the detection of systolic dysfunction by 2D speckle tracking.
In the present study, we showed that the global SI-DI was the strongest independent determinant of log10 NT-proBNP compared to conventional echocardiographic parameters. We examined patients with preserved ejection fraction in this study and diastolic dysfunction was considered to be a major factor contributing to elevated NT-proBNP. Conventional echocardiographic parameters using tissue Doppler imaging carry inherent limitations of tissue Doppler imaging. Tissue Doppler imaging is angle-dependent and is affected by tethering and myocardial translation. Other conventional echocardiographic parameters, such as the E/A ratio and deceleration time of the E-wave, have a limitation of pseudo-normalization, and are known to be inferior to those parameters using tissue Doppler imaging . In contrast, 2D speckle tracking echocardiography used for determining the SI-DI offers advantages over the Doppler-derived parameters given their angle independence. In addition, the global SI-DI, using the average of strain measurements of the whole left ventricle, allows the assessment of the global LV diastolic function. These factors were considered to contribute to the advantage of the global SI-DI over conventional echocardiographic parameters.
In the current study, we used longitudinal strain analyses, although transverse strain was used in previous studies [15, 16]. This is because the reproducibility of longitudinal strain measurements was reported to be superior to those of other directional strain measurements . In addition, it was also reported that longitudinal strain was impaired earlier than other directional strain in hypertensive patients . The accuracy of transverse, longitudinal, or other directional SI-DI for assessing diastolic function needs further evaluation.
An important limitation of our study is that we did not measure tau or LV diastolic filling pressure by invasive methods. This was because cardiac catheterization was not indicated in our study population of asymptomatic patients from outpatient clinics. However, NT-proBNP has been reported to be strongly correlated with the filling pressure measured invasively . Thus, we believe that the global SI-DI might represent a good index of diastolic function in our population. Additional studies are needed that compare the global SI-DI with invasive measures of diastolic function.
In this study, strain analysis was performed using QLAB software. The ability of 2D speckle tracking using QLAB was validated in comparison with tagged cardiac magnetic resonance , and many investigations using 2D speckle tracking echocardiography with QLAB have been reported [21, 22, 23]. However, strain measurements using this software have not been well validated as far as we know. There is a need for further investigation in order to validate this method.
Although we excluded patients with regional LV wall motion abnormalities, we could not exclude patients with latent coronary artery disease. Thus, an effect of latent coronary artery disease on strain measurements cannot be ruled out.
The plasma NT-proBNP level could be significantly influenced by the estimated glomerular filtration rate (GFR) . Although we excluded patients with chronic renal failure, we regrettably did not examine the data on the estimated GFR in this study. However, previous investigations, conducted among similar patients to our study, showed the NT-proBNP level to be correlated with the pulmonary capillary wedge pressure measured by catheterization  and predicted cardiovascular outcome , making us confident of our results in this study.
The global strain imaging diastolic index (SI-DI) was an independent predictor of elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) in hypertensive patients with preserved ejection fraction. The global SI-DI may serve as a novel and sensitive indicator in asymptomatic hypertensive patients who are at risk of developing diastolic heart failure (HF).
This work was partially supported by a Grant-in-Aid for Scientific Research (20500427) from the Japan Society for the Promotion of Science (Masao Daimon), partially supported by a Grant-in-Aid for Scientific Research (20231501) from the Ministry of Health, Labour and Welfare (Masao Daimon), and was partially supported by a Grant for Scientific Research (097XDAA00141) from the Department of Health, Taipei City Government (Shuo-Ju Chiang and Betau Hwang). We are grateful to Ms. Mei-Hsiu Yeh and Ms. Maiko Hirano for their research assistance.
Conflict of interest
There is no relationship with any industry.