Background
Chronic ischemia related occult systolic dysfunction of the right ventricle is difficult to detect using traditional echocardiography. The aim of this study was to verify the diagnostic value of speckle-tracking echocardiography in proximal right coronary artery (pRCA) lesion–induced right ventricular (RV) occult dysfunction.
Methods
One hundred forty-two patients undergoing elective coronary angiography for suspected coronary artery disease were divided into two groups according to involvement of the right coronary artery. In further analysis, significant stenosis before the acute marginal branch was defined as pRCA involvement and compared with a control group. Global longitudinal strain and RV free wall longitudinal train (RVLS-FW) were measured using speckle-tracking echocardiography. Other traditional parameters to evaluate RV function were also measured.
Results
Eighty-seven patients in the right coronary artery group (61.2%) displayed significant decreases in the magnitudes of both global longitudinal strain (−13.65 ± 3.83% vs −15.69 ± 4.37%, P = .04) and RVLS-FW (−16.04 ± 5.4% vs −21.18 ± 4.6%, P = .04), independent of other parameters. Conversely, when focusing on pRCA involvement, only RVLS-FW showed significant attenuation in the group with pRCA involvement (−14.26 ± 4.32% vs −19.96 ± 4.8%, P = .001). On multivariate analysis, RVLS-FW was still independently lower in the group with pRCA involvement (odds ratio, 1.07; 95% confidence interval, 1.01–1.14; P = .02).
Conclusions
The results of this study show that RVLS-FW was independently impaired in patients with coronary artery disease with right coronary artery stenosis, especially with involvement of the acute marginal branches. RV strain can be used to detect occult RV dysfunction in patients with stable coronary artery disease.
Speckle-tracking echocardiography (STE) is an emerging technique to evaluate occult myocardial dysfunction with angle-independent characteristics. Regional strain is regarded as a feasible and reliable noninvasive tool in the assessment of regional left ventricular (LV) myocardial function. In recent years, an increasing number of studies have shown that regional strain plays an important role in detecting coronary artery disease (CAD). Among all parameters, territorial longitudinal and circumferential strain have been shown to exhibit the highest sensitivity and specificity. In addition, a novel speckle-tracking echocardiographic algorithm, Automated Function Imaging (GE Healthcare, Little Chalfont, United Kingdom), has improved the ease of application of LV longitudinal strain in the clinical setting.
Although right ventricular (RV) function has a strong impact on morbidity and mortality in patients with cardiopulmonary disease, a limited number of modalities are available to evaluate right heart function, because of the enormous attention given to the left ventricle. Although speckle-tracking imaging is used mainly for the left ventricle, it has recently been investigated for use in the right heart. Most studies have focused on congenital heart defects, pulmonary hypertension, pulmonary embolism, and right cardiomyopathy, and only a few have investigated the role of speckle-tracking in the evaluation of CAD. One study demonstrated that RV strain and strain rate were lower in patients with LV inferior wall myocardial infarctions with, versus without, RV infarction. Nevertheless, the measurement those investigators used was angle-dependent tissue Doppler myocardial imaging, and gold-standard diagnostic assessments such as coronary angiography were lacking. Previous research has shown that the occlusion of the proximal right coronary artery (pRCA) before acute marginal branch caused RV dysfunction and dilatation, whereas left anterior descending coronary artery occlusion–induced small RV infarction rarely resulted in hemodynamic disturbance. In addition, neither LV global longitudinal strain (GLS) nor RV functional parameters can precisely predict specific coronary artery involvement, especially right coronary artery (RCA) lesions. Because RCA supplies the most blood to the RV free wall, in this study, we evaluated the diagnostic value of segmental longitudinal strain in patients with RV involvement related to RCA or pRCA lesions. We hypothesized that longitudinal strain might be an ideal parameter to detect occult RV systolic dysfunction, induced by ischemia, in patients with stable angina.
Methods
Subjects
One hundred seventy outpatients with stable angina who underwent elective coronary angiography were originally recruited. CAD was diagnosed by coronary angiography with significant coronary stenosis (>50% diameter stenosis measured by quantitative coronary angiography), and echocardiography was performed before the procedure. The exclusion criteria were acute and prior myocardial infarction, significant valvular heart disease (greater than moderate severity), moderate or severe pulmonary hypertension (> 50 mm Hg), pulmonary thromboembolic disease, atrioventricular block, unstable hemodynamics (systolic blood pressure < 90 mm Hg), and pericardial disease. Patients were divided into two groups according to the involvement of the RCA (RCA+ and RCA−). In further analysis, patients with significant stenosis involving the pRCA before a major acute marginal branch were defined as having pRCA involvement (pRCA+; Figure 1 ), and those without RCA disease or lesions distal to a major acute marginal branch were defined as the control group (pRCA−).
Echocardiography
Standard echocardiography was performed (Vivid 7; GE Vingmed Ultrasound AS, Horten, Norway) with a 3.5-MHz multiphase-array probe according to the recommendations of the American Society of Echocardiography. The chamber dimensions and LV mass were measured using the two-dimensionally guided M-mode method, and LV ejection fraction was measured using the biplane Simpson’s method. RV fractional area change was measured in an apical four-chamber view. Transmitral Doppler flow velocity was obtained from an apical four-chamber view, and peak early filling velocity (E), peak atrial velocity (A), and the E/A ratio were recorded. Peak systolic pulse Doppler tissue imaging was performed at the tricuspid annulus (S′). In addition, early diastolic annular velocity (E′) and atrial annular velocity (A′) were also measured to estimate LV end-diastolic pressure (E/E′ ratio). Tricuspid annular plane systolic excursion was also measured. Echocardiographic readers who analyzed the data were blinded to the results of coronary angiography.
Speckle-Tracking Echocardiographic Analysis for Deformation
Standard apical four-chamber, two-chamber, and three-chamber views were recorded in digital loops for deformation analysis of the left ventricle, and an apical four-chamber view focused on the right ventricle was used for RV deformation. The images were acquired with frame rates of 70 to 90 frame/sec and stored for three cycles. The images were analyzed offline using computer software (EchoPAC 09; GE Vingmed Ultrasound AS). For STE of the left ventricle, we used an automated imaging function, as described previously. In brief, analysis was performed for each of the apical views, with the operator identifying three points: two on each side of the mitral valve and a third at the apex of the left ventricle. The software automatically detected the endocardium and tracked myocardial motion during the entire cardiac cycle. U-shaped regions of interest were created on all three apical views, and the width of the region of interest was adjusted to cover the whole thickness of the LV wall. The software checked the tracking quality within the region of interest, and we double-checked visually. GLS and segmental longitudinal strain were then calculated automatically by the software after identifying the timing of aortic valve closure. The left ventricle was divided into 17 segments, and peak systolic longitudinal strain of each segment was obtained. GLS was calculated as the average of the 17 LV segments. RV deformation was measured by two-dimensional STE. RV free wall longitudinal strain (RVLS-FW) and strain rate were the averages of three segments in the RV free wall from the apical four-chamber view ( Figure 2 ).
In addition, to analyze the diagnostic impact of strain and other echocardiographic parameters in different populations, patients were further divided on the basis of old age (>60 years), medical history of hypertension, or diabetes.
Reproducibility
To assess intraobserver and interobserver variability, strain parameters were reevaluated using Bland-Altman limits of agreement and interclass correlation coefficients. Data from a total of 20 patients, identified randomly, were analyzed by two readers; each variable was measured in at 15-min intervals three separate times. Readers could select the best cardiac cycle by themselves and were blinded to previous measurements. The average value was used to test reproducibility. In addition to the interclass correlation coefficients for RVLS-FW and GLS, the mean intraobserver and interobserver differences as well as the absolute difference ratio (absolute difference between measurements divided by the mean of the repeated observations) were also calculated.
Statistical Analysis
Differences between groups were compared using independent t tests for continuous variables and χ 2 tests for categorical variables. Significant factors in univariate analysis were entered into the multivariate analysis. Multivariate logistic regression analysis was used to identify the independent RV strain parameters associated with RCA or pRCA involvement. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff values of RV strain in patients with or without RCA lesions involving the right ventricle. The best cutoff value was defined as the point with the highest sum of sensitivity and specificity. All data are presented as mean ± SD. P values < .05 were considered statistically significant. All analyses were performed with SPSS version 18 for Windows (SPSS, Inc, Chicago, IL).
Results
Differences between Patients with and without RCA Lesions
After excluding 10 (5.8%) and 18 (10.5%) patients because of suboptimal image quality and nonobstructive coronary angiographic finding, respectively, the remaining 142 patients (mean age, 63.67 ± 11.47 years; 113 men) were entered for analysis. Among them, 87 (61.2%) had RCA lesions. Comparing patients with RCA lesions and the control group, patients with RCA lesions tended to be male (85.1% vs 70.9%, P = .054), to have diabetes (49.4% vs 32.7%, P = .057), and to have undergone percutaneous intervention (75.6% vs 56.4%, P = .001) or bypass surgery (18.6% vs 1.8%, P = .001) ( Table 1 ).
| Variable | RCA+ ( n = 87 [61.2%]) | RCA− ( n = 55 [38.8%]) | P |
|---|---|---|---|
| Demographic characteristics | |||
| Age (y) | 63.67 ± 12 | 63.67 ± 11 | .99 |
| Men | 74 (85%) | 39 (71%) | .05 |
| Medical history | |||
| Diabetes mellitus | 43 (49.4%) | 18 (32.7%) | .05 |
| Hypertension | 69 (79.3%) | 39 (70.9%) | .31 |
| Smoking | 16 (18.4%) | 7 (12.7%) | .48 |
| Hyperlipidemia ∗ | 49 (56.3%) | 27 (49.1%) | .49 |
| Systolic blood pressure (mm Hg) | 148.15 | 135.14 | .18 |
| Diastolic blood pressure(mm Hg) | 75.94 | 69.42 | .2 |
| Coronary angiography and revascularization | |||
| Left main coronary artery | 12 (13.79%) | 10 (18.18%) | .12 |
| LAD | 60 (68.8%) | 28 (50.9%) | .08 |
| LCX | 54 (62%) | 27 (49.1%) | .1 |
| Percutaneous coronary intervention | 65 (75.6%) | 31 (56.4%) | .001 |
| Coronary bypass grafting | 16 (18.6%) | 1 (1.8%) | .001 |
| Laboratory measure at baseline | |||
| Glucose (mg/dL) | 118.78 | 125.71 | .65 |
| Creatinine (mg/dL) | 1.3 | 1.14 | .57 |
| Low-density lipoprotein (mg/dL) | 102.21 | 107.85 | .75 |
| Echocardiographic characteristics | |||
| Left heart parameters | |||
| LVEF (%) † | 59.72 ± 14.77 | 62.36 ± 14.62 | .3 |
| GLS (%) | −13.65 ± 3.83 | −15.69 ± 4.37 | .04 |
| LV mass index (g/m 2 ) | 182.99 ± 60.35 | 192.17 ± 64.75 | .52 |
| E/A ratio | 1.06 ± 0.71 | 0.93 ± 0.51 | .24 |
| E′ (cm/sec) | 6.9 ± 2.2 | 7.4 ± 4.97 | .16 |
| E/E′ ratio | 12.69 ± 7.02 | 11.22 ± 5.67 | .19 |
| Right heart parameters | |||
| Estimated PASP (mm Hg) | 26.2 ± 8.91 | 25 ± 8.65 | .45 |
| RV FAC (%) | 68.65 ± 13 | 71.21 ± 14.41 | .27 |
| TAPSE (cm) | 1.85 ± 0.5 | 2.01 ± 0.46 | .05 |
| S′ (cm/sec) | 11.84 ± 2.35 | 12.5 ± 2.37 | .09 |
| RVLS-FW (%) | −16.04 ± 5.4 | −21.18 ± 4.6 | .04 |
| RVLSR-FW (%) | −1.6 ± 0.57 | −1.7 ± 0.33 | .28 |
∗ Defined according to Third Adult Treatment Panel guidelines as total cholesterol > 240 mg/dL or triglyceride > 200 mg/dL.
With regard to the general echocardiographic parameters, LV ejection fraction, diastolic pressure, RV systolic pressure, and chamber dimensions were not significantly different between the RCA+ and RCA− groups. For RV function, there were no differences in RV fractional area change (68.65 ± 13% vs 71.21 ± 14.41%, P = .27), tricuspid annular plane systolic excursion (1.85 ± 0.5 vs 2.01 ± 0.46 cm, P = .053), or S′ (11.9 ± 2.3 vs 12.2 ± 2.2 cm/sec, P = .097) relating to RCA involvement. However, both right and left deformation markers, GLS (−13.65 ± 3.83% vs −15.69 ± 4.37%, P = .04) and RVLS-FW (−16.04 ± 5.4% vs −21.18 ± 4.6%, P = .04) were significantly impaired in the RCA+ group ( Table 1 ). Conversely, when focusing on pRCA involvement, only RVLS-FW showed significant attenuation in the pRCA+ group (−14.26 ± 4.32% vs −19.96 ± 4.8%, P = .01) ( Table 2 ).
| Variable | pRCA+ ( n = 59 [41.5%]) | pRCA− ( n = 83 [58.4%]) | P |
|---|---|---|---|
| Demographic characteristics | |||
| Age (y) | 63.27 ± 11.42 | 64.24 ± 12.21 | .62 |
| Men | 8 (13.6%) | 21 (25.3%) | .06 |
| Medical history | |||
| Diabetes mellitus | 30 (50.6%) | 31 (37.8%) | .07 |
| Hypertension | 45 (76.3%) | 63 (74.9%) | .56 |
| Smoking | 11 (18.6%) | 12 (14.5%) | .32 |
| Hyperlipidemia ∗ | 34 (57.6%) | 42 (50.2%) | .25 |
| Systolic blood pressure (mm Hg) | 133.5 ± 21.91 | 135.07 ± 18.99 | .94 |
| Diastolic blood pressure(mm Hg) | 75.62 ± 11.56 | 76.93 ± 10.77 | .31 |
| Coronary angiography and revascularization | |||
| Left main coronary artery | 9 (15.25%) | 13 (15.66%) | .18 |
| LAD | 43 (72.8%) | 46 (55.4%) | .06 |
| LCX | 38 (64.4%) | 44 (53%) | .08 |
| Three-vessel disease | 34 (57.6%) | 25 (30.1%) | .06 |
| Percutaneous coronary intervention | 43 (72.9%) | 53 (64.6%) | .19 |
| Coronary bypass grafting | 12 (20.3%) | 5 (6%) | .05 |
| Laboratory measure at baseline | |||
| Glucose (mg/dL) | 112.57 ± 27.62 | 113.06 ± 29.57 | .58 |
| Creatinine (mg/dL) | 1.21 | 1.14 | .27 |
| Low-density lipoprotein (mg/dL) | 114.56 ± 31.78 | 117.16 ± 28.11 | .93 |
| Echocardiographic characteristics | |||
| Left heart parameters | |||
| LVEF (%) † | 60.34 ± 14.77 | 61.03 ± 14.76 | .78 |
| GLS (%) | −14.09 ± 3.88 | −14.69 ± 4.34 | .39 |
| LV mass index (g/m 2 ) | 188.9 ± 64.96 | 184.87 ± 60.19 | .7 |
| E/A ratio | 1.06 ± 0.71 | 0.93 ± 0.51 | .24 |
| E′ (cm/sec) | 6.11 ± 2.23 | 7.11 ± 2.29 | .16 |
| E/E′ ratio | 14.22 ± 7.9 | 12.08 ± 6.07 | .19 |
| Right heart parameters | |||
| Estimated PASP (mm Hg) | 26.23 ± 9.61 | 25.4 ± 8.22 | .6 |
| RV FAC (%) | 68.17 ± 12 | 70.68 ± 14.55 | .28 |
| TAPSE (cm) | 1.81 ± 0.49 | 1.99 ± 0.47 | .08 |
| S′ (cm/sec) | 11.96 ± 2.36 | 12.21 ± 2.39 | .53 |
| RVLS-FW (%) | −14.26 ± 4.32 | −19.96 ± 4.8 | .01 |
| RVLSR-FW (%) | −1.73 ± 0.47 | −1.94 ± 0.54 | .09 |
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