Background
To understand the influence of myocardial bridging (MB) on left ventricular (LV) function, myocardial function was studied in patients with MB of the left anterior descending coronary artery (LAD) using three-dimensional speckle-tracking echocardiography (STE).
Methods
Left anterior descending coronary artery MB was diagnosed by coronary angiography in 82 subjects. Patients were divided into three groups according to the percentage of systolic narrowing of the compressed segment: 30% to 49% was defined as group I (24 patients), 50% to 74% as group II (28 patients), and ≥75% as group III (30 patients). Thirty gender- and age-matched normal subjects were included as controls. Left ventricular myocardial deformation was estimated by three-dimensional STE.
Results
Left ventricular ejection fractions were normal in all patients, but diastolic function was impaired in groups II and III (E/E′ ratio, 9 ± 3 and 10 ± 3, respectively). The amplitudes of longitudinal strain (LS) and area strain (AS) of the LAD territory was significantly reduced in groups II and III compared with controls and group I (LS, −15 ± 2% and −12 ± 1% vs −19 ± 2% and −18 ± 2%; AS, −22 ± 2% and −13 ± 2% vs −33 ± 4% and −33 ± 3%; P < .0001), but the amplitudes of circumferential and radial strain showed no intergroup differences. Longitudinal strain and AS were significantly lower in patients with fractional flow reserve < 0.75 than in those with fractional flow reserve ≥ 0.75 ( P < .0001), with relative preservation of circumferential and radial strain. The severity of LAD compression was significantly associated with AS and LS of the LAD territory ( r = −0.92 and r = −0.84, respectively, P < .0001), but the correlations with circumferential and radial strain were modest ( r = −0.36 and r = −0.32, respectively, P < .05).
Conclusions
With the increasing severity of systolic compression of the mural coronary artery, LV diastolic function and regional systolic deformation (AS and LS) of the MB perfusion territory were reduced. Three-dimensional STE can detect subtle myocardial dysfunction in patients with MB.
Myocardial bridging (MB) is the term used to describe an intramural segment of a coronary artery that is associated with focal systolic compression of the vessel. MB is usually confined to the mid left anterior descending coronary artery (LAD). Recent studies have suggested that MB might be more frequent than previously thought, with the reported incidence varying from 1.5% to 16%. In the past, MB was considered to be a benign condition. However, recent studies assessing coronary fractional flow reserve (FFR) suggested that MB could impair coronary flow and lead to clinical syndromes such as angina, myocardial stunning, infarction, arrhythmia, and sudden death. Despite the improved understanding of the hemodynamic effects of MB, its impact on myocardial function remains unclear.
Speckle-tracking echocardiography (STE) has been increasingly used for the evaluation of myocardial deformation (strain). Two-dimensional (2D) STE is commonly used, but the evaluation of strain in 2D planes is often limited by apical foreshortening and geometric assumptions, which may result in inaccurate representations of true mechanical function. Three-dimensional (3D) STE is a novel method to characterize and quantify myocardial deformation ; 3D STE has overcome the limitations of 2D STE and is capable of providing simultaneous comprehensive evaluation of 17 left ventricular (LV) segments in a single beat by measuring the values of myocardial strain in multiple directions, including longitudinal strain (LS), circumferential strain (CS), radial strain (RS), and area strain (AS). The aim of this study was to evaluate the global and regional LV function in patients with isolated MB of LAD using 3D STE.
Methods
Study Population
We prospectively evaluated 4,680 consecutive patients who underwent angiography for chest discomfort. Among them, 94 patients were diagnosed with isolated LAD MB without any significant atherosclerosis; the prevalence of LAD MB was thus about 2.0%. Another 30 gender- and age-matched normal subjects were studied as controls. All eligible subjects underwent physical examination, electrocardiography, and transthoracic echocardiography. Exclusion criteria were (1) atrial fibrillation, (2) hemodynamic and electrical instability, (3) structural heart disease, (4) hypertrophic cardiomyopathy, (5) atherosclerotic coronary stenosis, and (6) suboptimal echocardiographic window. All study subjects provided informed consent before enrolment. The study protocol was approved by the local institution research ethics committees.
Coronary Angiography
All patients underwent coronary angiography using standard procedures. The typical angiographic finding in MB of the LAD is transient systolic compression of the mural coronary artery (in the form of linear, beaded stenosis or even complete occlusion), while a persistent compression in systole is known as the “milking effect.” Quantification of systolic compression was performed using a programmable digital caliper to measure the systolic luminal diameter reduction. To find an absolute reduction in systolic coronary artery dimensions, each coronary study was repeated after nitroglycerin injection. Isolated MB was defined as >30% systolic LAD diameter reduction without any significant atherosclerosis ( Figure 1 ). The length and thickness of the myocardial bridge were measured by intravascular ultrasound. Each angiogram was reviewed by at least two experienced cardiologists, who measured coronary luminal diameters blinded to each other’s measurements. The results were accepted only when the disparity between the measurements of the two cardiologists was <10%.
Fractional Flow Reserve Measurement with Dobutamine Challenge
Functional significance of the myocardial bridge in all patients was assessed with FFR measurement during dobutamine infusion challenge. Aortic pressure was obtained by using a 6-F guiding catheter without side holes, connected to a pressure transducer and to a Horizon 9000 computerized polygraph (Mennen Medical, Inc, Haifa, Israel). Intracoronary pressure measurement was performed using a 0.014-inch pressure wire (Radi Medical Systems, Uppsala, Sweden). Distal pressure was obtained by a pressure sensor, which was located approximately 3 cm distal to the myocardial bridge to avoid its entrapment and direct compression by the bridge. Dobutamine was infused at a starting dose of 5 μg/kg/min and then increased by 5 μg/kg/min every 3 min to a maximum of 40 μg/kg/min. Dobutamine infusion was discontinued when the patient developed symptoms. FFR was defined as the ratio between pressures measured distal to and proximal the myocardial bridge during maximal hyperemia (FFR = distal pressure/aortic pressure).
Standard Echocardiography
All participants underwent standard 2D and Doppler echocardiography (Vivid E9; GE Healthcare, Milwaukee, WI) using a 2.5-MHz transducer. Images were obtained at a frame rate of 60 to 75 frames/sec and digitally transferred to a remote workstation for offline analysis (EchoPAC; GE Medical Systems, Milwaukee, WI). Parasternal images were used to determine LV dimensions and relative wall thickness. LV mass was calculated from LV linear dimensions in the parasternal view and was indexed to body surface area to derive the LV mass index. Pulsed-wave Doppler recording of mitral inflow was performed by placing a 2.5-mm sample volume at the tip of the mitral valve leaflets. The peak velocities of early (E) and atrial (A) diastolic filling, MV deceleration time, and isovolumic relaxation time were measured, and the E/A ratio was calculated. E′ was the mean value of the mitral annular velocities measured at the septal and lateral annuli by Doppler tissue imaging. The E/E′ ratio was calculated by dividing early mitral inflow velocity (E) by early diastolic mitral annular velocity (E′).
Three-Dimensional STE
Three-dimensional echocardiography was performed using a 4V matrix-array transducer (Vivid E9). Gain, compression, and time-gain compensation settings were optimized to enhance image quality. Single-beat full-volume images were acquired from a single cardiac cycle at end-expiration breath-hold. The full-volume data of the left ventricle were displayed in the four-, three-, and two-chamber and the three short-axis views. Endocardial borders for end-diastole and end-systole were defined by marking the midpoint of the mitral annular plane and the LV apex. 4D Auto LVQ software (GE Medical Systems) automatically tracked the endocardial and epicardial contours through the entire cardiac cycle. The tracing was manually modified if necessary. Then the software automatically calculated LV end-diastolic volume, LV end-systolic volume, and LV ejection fraction (LVEF), as well as the peak global and segmental LS, CS, RS, and AS ( Figure 2 ). The user interface allows manual rejection of segments with suboptimal tracking.
The left ventricle was divided into 17 myocardial segments according to the territories supplied by the LAD, right coronary artery, and left circumflex coronary artery. We defined the basal and mid anterior wall and anteroseptum, apical anterior and septal segments, as well as the apical cap as the territory supplied by the LAD; the basal and mid inferolateral and anterolateral wall and apical lateral wall as left circumflex coronary artery territory; and the basal and mid inferior and inferoseptal wall and apical inferior wall as right coronary artery territory.
Reproducibility Analysis
Intra- and interobserver variability of 3D speckle-tracking echocardiographic measurements was assessed by two sonographers in 20 randomly selected subjects. To obtain interobserver variability, images were analyzed by a second observer blinded to the values obtained by the first observer. Intraobserver variability was assessed by repeating analysis at a different time by an observer blinded to the previous measurements. Interobserver variability of systolic compression measurement on coronary angiography was also assessed by two observers.
Statistical Analysis
Statistical analysis was performed using SPSS version 17.0 (SPSS, Inc, Chicago, IL). Continuous variables are expressed as mean ± SD and categorical variables as percentages. Continuous variables among groups were compared by analysis of covariance in a general linear model with least significantly different post hoc analysis. Comparisons between patients with FFR < 0.75 and those with FFR ≥ 0.75 were assessed by independent-samples t tests. Correlations between strain variables and the severity of MB were analyzed using linear regression analysis. Intra- and interobserver variability was evaluated using the coefficient of variation (defined as the absolute difference between the two sets of measurements divided by the mean of the measurements) and the intraclass correlation coefficient. P values < .05 were considered to indicate statistical significance.
Results
Patient Characteristics
Among the 94 screened patients, four were excluded because of disagreement of >10% on quantitative coronary angiography by the two observers, six were excluded because of poor quality of echocardiographic images, and two were excluded because of too many segments with poor tracking. The remaining 82 patients were divided into three groups according to the percentage of systolic compression of the mural LAD: group I, with systolic compression of 30% to 49% ( n = 24); group II, with systolic compression of 50% to 74% ( n = 28); and group III, with systolic compression of ≥75% ( n = 30). There were no significant differences in clinical characteristics among all three groups ( Table 1 ). The lengths and locations of myocardial bridges were similar among groups, but there was a significant intergroup difference in the thicknesses of myocardial bridges ( P < .0001) ( Table 2 ).
| Variable | Normal controls ( n = 30) | Group I ( n = 24) | Group II ( n = 28) | Group III ( n = 30) | P (ANOVA) |
|---|---|---|---|---|---|
| Age (y) | 52 ± 6 | 53 ± 8 | 52 ± 8 | 54 ± 6 | NS |
| Men | 50% | 51% | 49% | 49% | NS |
| BMI (kg/m 2 ) | 22 ± 7 | 23 ± 6 | 24 ± 9 | 22 ± 6 | NS |
| Heart rate (beats/min) | 74 ± 9 | 76 ± 9 | 77 ± 5 | 79 ± 6 | NS |
| Systolic blood pressure (mm Hg) | 120 ± 11 | 122 ± 16 | 118 ± 18 | 121 ± 12 | NS |
| Diastolic blood pressure (mm Hg) | 73 ± 9 | 77 ± 9 | 78 ± 10 | 80 ± 8 | NS |
| Total cholesterol (mmol/L) | 4.56 ± 1.23 | 4.62 ± 1.35 | 4.59 ± 1.29 | 4.67 ± 0.79 | NS |
| Triglyceride (mmol/L) | 1.35 ± 0.23 | 1.27 ± 0.41 | 1.29 ± 0.28 | 1.39 ± 0.51 | NS |
| HDL cholesterol (mmol/L) | 1.38 ± 0.35 | 1.28 ± 0.67 | 1.31 ± 0.78 | 1.36 ± 0.52 | NS |
| LDL cholesterol (mmol/L) | 2.38 ± 0.68 | 2.52 ± 0.77 | 2.49 ± 0.14 | 2.55 ± 0.36 | NS |
| Variable | Group I ( n = 24) | Group II ( n = 28) | Group III ( n = 30) | P (ANOVA) |
|---|---|---|---|---|
| Location of MB | ||||
| Proximal LAD (%) | 1 (4%) | 2 (7%) | 1 (3%) | NS |
| Mid LAD (%) | 20 (83%) | 23 (82%) | 25 (83%) | NS |
| Distal LAD (%) | 3 (13%) | 3 (11%) | 4 (14%) | NS |
| Length of MB (mm) | 22.4 ± 7.5 | 23.8 ± 9.8 | 24.1 ± 11.3 | NS |
| Thickness of MB (mm) | 1.5 ± 0.6 | 2.2 ± 0.9 ∗ | 3.1 ± 1.0 ∗ , † | <.0001 |
∗ P < .05 compared with group I.
Standard Echocardiography
The parameters of 3D and 2D echocardiography are listed in Table 3 . Three-dimensional LVEFs were normal in all patients. LVEFs were lower in groups II and III than in group I and controls. The E/A ratio and E′ were lower and E/E′, deceleration time, and isovolumic relaxation time higher in groups II and III than in group I and controls ( P < .0001), indicating that LV diastolic function was impaired in groups II and III.
| Variable | Normal controls ( n = 30) | Group I ( n = 24) | Group II ( n = 28) | Group III ( n = 30) | P (ANOVA) |
|---|---|---|---|---|---|
| 3D LVEDV (mL) | 75 ± 10 | 76 ± 11 | 78 ± 10 | 78 ± 12 | NS |
| 3D LVESV (mL) | 27 ± 7 | 28 ± 8 | 31 ± 9 ∗ , † | 35 ± 10 ∗ , † , ‡ | <.0001 |
| 3D LVSV (mL) | 48 ± 9 | 48 ± 10 | 47 ± 10 | 43 ± 11 ∗ , † , ‡ | <.0001 |
| 3D LVEF (%) | 65 ± 6 | 63 ± 5 | 59 ± 5 ∗ , † | 55 ± 6 ∗ , † , ‡ | <.0001 |
| LVMI (g/m 2 ) | 98 ± 16 | 101 ± 23 | 96 ± 20 | 98 ± 17 | NS |
| Mitral E (cm/sec) | 72 ± 12 | 70 ± 12 | 65 ± 14 ∗ , † | 59 ± 13 ∗ , † , ‡ | <.0001 |
| Mitral A (cm/sec) | 64 ± 10 | 62 ± 11 | 67 ± 10 | 67 ± 11 | NS |
| Mitral E/A | 1.1 ± 0.4 | 1.1 ± 0.3 | 0.9 ± 0.6 ∗ , † | 0.8 ± 0.4 ∗ , † | <.0001 |
| E′ (cm/sec) | 9.7 ± 3.0 | 9.4 ± 2.7 | 7.1 ± 2.1 ∗ , † | 6.0 ± 2.8 ∗ , † , ‡ | <.0001 |
| E/E′ | 7.4 ± 2.6 | 7.5 ± 2.1 | 9.2 ± 2.8 ∗ , † | 9.8 ± 2.5 ∗ , † | <.0001 |
| DT (sec) | 185 ± 38 | 190 ± 23 | 194 ± 30 ∗ , † | 215 ± 36 ∗ , † , ‡ | <.0001 |
| IVRT (sec) | 85 ± 18 | 87 ± 22 | 96 ± 21 ∗ , † | 101 ± 26 ∗ , † , ‡ | <.0001 |
∗ P < .05 compared with normal controls.
† P < .05 compared with group I.
Parameters of Strain by 3D STE among the Study Groups
All 3D strain variables are listed in Table 4 . The average amplitudes of peak LS and AS of the LAD territory were significantly reduced in groups II and III compared with controls and group I ( P < .05), but the amplitudes of CS and RS were relatively preserved in the three MB groups compared with controls ( P > .05 for all) ( Figure 2 ). Similarly, global LS and AS, but not CS and RS, were significantly reduced in the MB groups.
| Normal controls ( n = 30) | Group I ( n = 24) | Group II ( n = 28) | Group III ( n = 30) | P (ANOVA) | |
|---|---|---|---|---|---|
| LS (%) | |||||
| LAD | −18.5 ± 1.6 | −18.0 ± 2.0 | −15.1 ± 1.5 ∗ , † | −12.0 ± 1.4 ∗ , † , ‡ | <.0001 |
| RCA | −17.9 ± 1.6 | −17.4 ± 2.1 | −17.1 ± 1.7 | −17.1 ± 1.4 | NS |
| LCX | −17.8 ± 1.5 | −17.6 ± 1.8 | −17.2 ± 1.6 | −17.0 ± 1.2 | NS |
| Global | −18.1 ± 0.8 | −17.6 ± 1.0 | −16.1 ± 0.7 ∗ , † | −14.9 ± 0.9 ∗ , † , ‡ | <.0001 |
| RS (%) | |||||
| LAD | 55.5 ± 6.5 | 54.3 ± 3.3 | 54.0 ± 4.5 | 52.9 ± 5.1 | NS |
| RCA | 55.7 ± 6.2 | 55.7 ± 6.5 | 53.6 ± 5.3 | 54.1 ± 4.6 | NS |
| LCX | 54.6 ± 7.3 | 52.4 ± 5.0 | 54.4 ± 5.3 | 53.6 ± 6.0 | NS |
| Global | 55.2 ± 4.0 | 54.1 ± 2.8 | 54.0 ± 3.0 | 53.6 ± 4.2 | |
| CS (%) | |||||
| LAD | −19.8 ± 1.2 | −19.7 ± 1.4 | −19.6 ± 1.1 | −19.1 ± 1.1 | NS |
| RCA | −19.9 ± 1.6 | −19.4 ± 1.7 | −19.6 ± 1.2 | −19.7 ± 1.0 | NS |
| LCX | −20.5 ± 1.6 | −20.0 ± 1.4 | −−20.1 ± 1.8 | −20.0 ± 0.9 | NS |
| Global | −19.9 ± 0.8 | −19.8 ± 0.9 | −19.8 ± 0.8 | −19.6 ± 0.8 | NS |
| AS (%) | |||||
| LAD | −32.6 ± 4.0 | −33.1 ± 3.0 | −21.5 ± 2.0 ∗ , † | −13.0 ± 1.5 ∗ , † , ‡ | <.0001 |
| RCA | −32.8 ± 4.0 | −33.4 ± 3.2 | −33.3 ± 3.6 | −31.8 ± 3.1 | NS |
| LCX | −34.8 ± 4.3 | −33.6 ± 3.6 | −33.4 ± 3.6 | −33.1 ± 3.5 | NS |
| Global | −33.4 ± 2.2 | −33.3 ± 1.7 | −28.2 ± 1.7 ∗ , † | −24.6 ± 1.8 ∗ , † , ‡ | <.0001 |
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