Left ventricular (LV) ejection fraction (LVEF) is the most common echocardiographic parameter to assess systolic LV function. However, this volumetric measurement has several limitations, such as high load dependence and low sensitivity to determine subtle LV systolic dysfunction. Because of these limitations, research into new and more sensitive systolic parameters has been of significant interest in recent years. Several studies using two-dimensional (2D) speckle-tracking echocardiography (STE) have demonstrated that despite normal LVEF, many patients in different clinical settings have longitudinal systolic dysfunction of the left ventricle. Thus, systolic analysis of the left ventricle using global longitudinal systolic strain has been suggested as a new standard assessment for global LV systolic function. Nevertheless, more recent studies have demonstrated that the global systolic function of the left ventricle is the result of multidirectional contractions in longitudinal, circumferential, and radial directions. In addition, several studies have found heterogeneous systolic alterations of the left ventricle (in the longitudinal, radial, and circumferential directions) in diverse clinical settings such as diabetes, hypertension, LV hypertrophy, coronary artery disease, and heart failure. Therefore, analyzing only a unidirectional function (i.e., longitudinal, radial, or circumferential) would merely be a partial approach to assess true global LV systolic function.

Recent findings in a small group of patients suggested that using multidirectional systolic parameters such as a global systolic index (average of longitudinal, circumferential, and radial global systolic strain), it is possible to detect an alteration in multidirectional global LV contractile function in patients with heart failure. However, despite these advances in multidirectional parameters to determine true global LV systolic function, the normal ranges and the clinical relevance of these multidirectional indices remain poorly understood. Therefore, the aim of this multicenter study was to establish the range of values of these multidirectional measurements in the healthy population and to demonstrate if these multidirectional indices provide improved detection of LV global systolic dysfunction in patients with a common condition such as hypertension.

Methods

Healthy Population

We enrolled healthy subjects ≥18 years of age prospectively included at nine centers in Japan and one center in Germany. These subjects were part of the Japanese Ultrasound Speckle Tracking of the Left Ventricle Research Project, which enrolled healthy volunteers subjects at different university hospitals and was endorsed by the Japanese Society of Echocardiography. Healthy subjects were defined as all those with absence of disease or cardiovascular risk factors such as obesity (body mass index ≥ 30 kg/m ² ), diabetes (fasting plasma glucose ≥ 126 mg/dL), hypertension (systolic and diastolic blood pressure ≥ 140/90 mm Hg), and hypercholesterolemia (fasting plasma low-density lipoprotein cholesterol ≥ 160 mg/dL); no medications; and normal results on echocardiography according to the diagnostic criteria of the American Society of Echocardiography. The ethics committee of each of the hospitals approved this research project, and informed consent was obtained from all subjects.

Hypertensive Patient Cohort

To determine the clinical relevance of multidirectional systolic parameters to evaluate global LV systolic function, we analyzed a cohort of patients with hypertension included in previous studies of our research group. Hypertension was defined as systolic and diastolic blood pressure ≥ 140/90 mm Hg and/or use of antihypertensive medications. To avoid causes of LV myocardial dysfunction other than hypertension, patients with coronary artery disease were excluded (namely, those with unstable angina or non–ST-segment elevation myocardial infarctions, ST-segment elevation acute myocardial infarctions, coronary artery bypass graft surgery, chronic stable angina, or evidence of myocardial ischemia assessed by stress echocardiography). Moreover, with the purpose of excluding causes of dyspnea or LV dysfunction other than hypertension, patients with the following characteristics were excluded: (1) severe pulmonary disease, defined as pulmonary pathology with requirement for supplemental oxygen or need for treatment with corticoids; (2) severe kidney disease, defined as estimated glomerular filtration rate < 30 mL/min/1.73 m ² for ≥3 months, history of renal transplantation, or severe acute renal failure with requirement for dialysis; (3) severe chronic liver disease or history of liver transplantation; (4) congenital heart disease; (5) pericardial disease characterized by moderate or severe pericardial effusion (echo-free space in end-diastole ≥ 5 mm) or constrictive pericarditis; (6) cardiomyopathy; and (7) valvular heart disease, defined as mild, moderate, or severe mitral or aortic stenosis, moderate or severe nonfunctional mitral or tricuspid regurgitation, and moderate or severe aortic regurgitation (according to the diagnostic criteria of the guidelines for the management of patients with valvular heart disease of the American College of Cardiology). Furthermore, to avoid underestimations of myocardial and mitral annular measurements, patients with valvular heart surgery, mitral annular calcification (≥5 mm), cardiac pacing, and poor 2D quality in one or more myocardial segments of the left ventricle (not suitable for analysis by 2D STE in the apical four-chamber, two-chamber, and long-axis views) were also excluded. In addition, to avoid mistakes or large variations in the myocardial measurements of the left ventricle due to variability of the R-R interval, patients with atrial or ventricular arrhythmias were also excluded.

Transthoracic Echocardiography

All subjects were examined at rest in the left lateral decubitus position using the Vivid 7 or Vivid E9 ultrasound system (GE Healthcare, Little Chalfont, United Kingdom). LV diameters, LV volumes, LV mass, LVEF (determined using Simpson’s method), and LV diastolic function were assessed as recommended by the American Society of Echocardiography. All echocardiographic measurements using 2D STE, Doppler, and conventional 2D echocardiography were calculated as the averages of three measurements. In addition, to avoid large variations in the myocardial analyses of the left ventricle, subjects with poor 2D imaging quality in one or more segments of the left ventricle were excluded from this study.

Two-Dimensional STE

The myocardial analyses by 2D STE were performed offline and blinded to the clinical characteristics of the subjects using EchoPAC version 113.0 (GE Healthcare). The analyses of LV longitudinal systolic strain were performed in the whole myocardium in the basal, middle, and apical segments in the apical four-chamber, two-chamber, and long-axis views (i.e., 18 segments of the left ventricle). The average value of peak systolic strain in the longitudinal direction from 18 LV segments was called LV global longitudinal systolic strain. Measurements of LV circumferential and radial systolic strain were performed in the entire myocardium in the three short-axis views of the left ventricle (basal, middle, and apical levels). The average values of peak systolic strain in the circumferential and radial directions from 18 LV segments were called LV global circumferential and radial systolic strain.

Multidirectional Global Systolic Function or Myocardial Systolic Performance of the Left Ventricle

Using 2D STE and the same 18-segment LV model used for the aforementioned measurements of LV global longitudinal, radial, and circumferential systolic strain, we assessed the multidirectional global systolic function of the left ventricle by means of two indices : (1) longitudinal-circumferential systolic index = average of longitudinal and circumferential global systolic strain, and (2) global systolic index = average of longitudinal, circumferential, and radial global systolic strain. Examples of how to perform these multidirectional measurements are shown in Figure 1 .

Analysis of multidirectional global systolic function or performance of the left ventricle by means of the global systolic index and the longitudinal-circumferential systolic index. The global systolic index is simply calculated as the average of longitudinal, circumferential, and radial global systolic strain, assuming, for practical purpose, all strain values as positive; thus, in this case, global systolic index = (38 + 22 + 24)/3 = 28. Moreover, it is important to know that specifically the global systolic index can also be calculated as [(global radial systolic strain) − (global longitudinal systolic strain + global circumferential systolic strain)]/3; namely, to average negative and positive values, one must subtract the negative value of the global longitudinal and circumferential strain from the positive value of the global radial stain; thus, in the same case, global systolic index = {38 − [(−22) + (−24)]}/3 = [38 − (−46)]/3 = 84/3 = 28. The longitudinal-circumferential systolic index is simply calculated as the average of the longitudinal and circumferential global systolic strain; thus, in this case, longitudinal-circumferential systolic index = {[(−22) + (−24)]/2} = [(−46)/2] = −23.

Statistical Analysis

Continuous data are expressed as mean ± SD and dichotomous data as percentages. Differences in continuous variables between groups were analyzed using Student’s t test. Categorical variables were compared using χ ² and Fisher’s exact tests as appropriate. Comparisons among three or more groups were analyzed using one-way analysis of variance. The relationships of the global systolic index and the longitudinal-circumferential systolic index with continuous variables were analyzed using a simple regression analysis. In addition, to determine the variables with the strongest associations with these multidirectional indices, we performed a multivariate stepwise forward linear regression analysis. Following the recommendations on chamber quantification of the American Society of Echocardiography, the lowest expected values of both the global systolic index and the longitudinal-circumferential systolic index were calculated as −1.96 SDs from the mean. With the purpose of determining the reproducibility of the global systolic index and the longitudinal-circumferential systolic index, we analyzed the intraobserver and interobserver variability of these indices in 20 randomly selected subjects. All statistical analyses were performed using StatView version 5.0 (SAS Institute Inc, Cary, NC) and SPSS version 19.0 (IBM, Armonk, NY). Differences were considered statistically significant at P < .05.