Compared with previous three-dimensional (3D) echocardiographic scanners, high–volume rate scanners allow higher temporal resolution and the possibility of displaying cropped images side by side. These new features make 3D echocardiography (3DE) even more attractive for application during stress. The aim of this study was to compare the feasibility and diagnostic accuracy of high–volume rate 3DE with state-of-the-art two-dimensional echocardiography (2DE) in detecting ischemia during dipyridamole-induced stress (DipSE).
One hundred seven consecutive patients with known or suspected coronary artery disease were examined using 2DE and 3DE during the same DipSE examination.
Seventeen patients with inadequate images on 2DE requiring contrast infusion and 6 patients with inadequate detection of the endocardial borders on 3DE were excluded (feasibility of 3DE, 79%). The diagnostic accuracy of 3DE with DipSE was tested in the remaining 84 patients. Both acquisition time (65 ± 30 s vs 16 ± 3 seconds, respectively; P < .0001) and analysis time (176 ± 63 vs 91 ± 5 seconds, respectively; P < .0001) were significantly longer with 2DE than 3DE. Temporal resolution was significantly higher with 2DE than 3DE (75 ± 5 frames/s vs 41 ± 5 volumes/s, respectively; P < .0001). The wall motion score index (WMSI) at baseline was similar with 2DE and 3DE (1.041 ± 0.023 vs 1.049 ± 0.01, respectively; P = NS). In contrast, peak stress WMSI was significantly lower with 2DE than 3DE (1.21 ± 0.025 vs 1.29 ± 0.023, respectively; P = .011). In particular, mean apical peak stress WMSI was significantly lower with 2DE than 3DE (1.34 ± 0.057 vs 1.55 ± 0.078, respectively; P < .0001). In the 44 patients who underwent coronary angiography, the overall accuracy of 3DE was similar to that of 2DE (sensitivity, 80% vs 78%; specificity, 87% vs 91%). In the left anterior descending coronary artery territory, for which 3DE showed higher WMSI values, the sensitivity of 3DE was significantly higher than that of 2DE (87% vs 78%, P = .011), while specificity was similar.
Three-dimensional echocardiography with DipSE is feasible and offers shorter acquisition and analysis times compared with 2DE, with similar overall diagnostic accuracy. However, the ability of 3DE to identify wall motion abnormalities in the apical region explains its higher sensitivity for the left anterior descending coronary artery territory.
Two-dimensional (2D) stress echocardiography is a firmly established technique to detect the presence and severity of inducible ischemia and to assess prognosis in patients with known or suspected coronary artery disease. However, the 2D technique has important practical limitations in its application during stress, including the time required to acquire multiple views from different approaches and the operator-dependent image acquisition. In addition, conventional 2D quad-screen display encompasses only a limited portion of the left ventricular (LV) circumference, resulting in the potential risk for missing stress-induced wall motion abnormalities. Finally, the difficulty to exactly match myocardial segments between baseline and peak stress acquisitions may result in overestimation or underestimation of wall motion abnormalities, especially in patients with preexisting abnormalities.
Full-volume three-dimensional (3D) echocardiography (3DE) allows the operator to rapidly acquire images and to visualize the entire left ventricle in an unlimited number of planes simply by rotating and slicing the acquired volumetric data set. In addition, once a volumetric data set is acquired, proper and clear matching views for baseline and peak stress can easily be aligned for the comparison of the same LV segments. Finally, 3DE has been reported to shorten significantly the time required to perform stress echocardiography, making 3D stress echocardiography more cost-effective.
Although 3DE has the potential to become the technique of choice for the accurate detection of inducible ischemia during stress echocardiography, some concerns have been raised regarding the relatively low temporal resolution of the technique, the additional analysis time required to crop a full-volume data set, and the inability to display cropped images side by side both at baseline and during peak stress. Currently, 3D echocardiographic systems with higher temporal resolution at comparable volume size and equipped with specific software that allows automatic slicing and side by side comparison of cropped images are commercially available. Therefore, we designed this prospective study to evaluate the feasibility and efficacy of high–volume rate 3DE to detect ischemia during dipyridamole-induced stress (DipSE) and to compare the results with conventional 2D images acquired immediately before the 3D echocardiographic data set.
We studied 107 consecutive patients who were subjected to DipSE for known or suspected coronary artery disease. No patient was excluded on the basis of image quality. Patients were excluded only if they had rhythm disturbances that precluded the acquisition of electrocardiographically gated 3D full-volume data sets and/or contraindications to dipyridamole. The study protocol was approved by our institutional ethics committee, and all patients gave written informed consent.
Patients were studied in the left lateral decubitus position after establishing an intravenous line for dipyridamole infusion. Conventional 2D views (parasternal long-axis; parasternal short-axis at the papillary muscle level’ and 3 apical views: 4-chamber, 2-chamber, and long-axis) were acquired by an experienced investigator using a commercially available Vivid E9 ultrasound machine (GE Vingmed Ultrasound AS, Horten, Norway) equipped with an M5S probe using the grayscale second-harmonic 2D imaging technique, with adjustment of image contrast, frequency, depth, and sector size for adequate frame rate and optimal LV border visualization. Care was taken to avoid LV foreshortening in apical views, and image acquisition was done during breath hold to minimize respiratory movements.
Electrocardiography, blood pressure and oxygen saturation were continuously assessed using a commercially available monitoring system (Vitalogik 5000; Mennen Medical Ltd, Tel Aviv, Israel).
Data set acquisition of the left ventricle was performed by the same examiner at the end of the standard 2D examination, using the same echocardiographic scanner, by switching to a 3V matrix-array transducer (GE Vingmed Ultrasound AS). A full-volume scan was acquired using second-harmonic imaging from the apical approach, and care was taken to encompass the entire LV cavity in the data set by using the medium volume size to maintain adequate spatial resolution. Consecutive 4-beat electrocardiographically gated subvolumes were acquired during end-expiratory apnea to generate the full-volume data set. The quality of the acquisition was then verified in each patient by selecting 9-slice display mode available on the machine to ensure optimal imaging of the entire LV endocardium at each short-axis level, and if unsatisfactory, the data set was reacquired.
Both 2D cine loops and real-time 3D echocardiographic data sets were stored digitally in raw format and exported to a separate workstation equipped with commercially available software for offline analysis (EchoPAC PC version 108.1.4; GE Vingmed Ultrasound AS).
Patients were asked to avoid drinks containing xanthine for ≥48 hours before the study. Dipyridamole was infused at a dose of 0.84 mg/kg over 6 minutes, unless symptoms of intolerability, positivity for ischemia, major arrhythmias, or hypotension (>30 mm Hg decrease in blood pressure) occurred. Atropine was not used to increase heart rate. Two-dimensional and 3D echocardiographic acquisitions were performed by the same investigator at baseline, during peak stress (2 minutes after the end of dipyridamole infusion), and at recovery (2 minutes after teofilline infusion) by quickly switching between the 2D and 3D echocardiographic transducers ( Figure 1 ). The sequence of image acquisition by the two techniques was similar in all patients; that is, 3D echocardiographic data sets were obtained immediately after the 2D acquisitions.
LV Wall Motion Analysis
The left ventricle was divided into 17 segments assigned to coronary artery supply according to the European Association of Echocardiography. Image analysis was performed by an experienced echocardiographer (L.P.B.) unaware of patients’ clinical and angiographic data, who analyzed stored 2D cine loops and 3D echocardiographic data sets in random order (the reader did not know which 2D recording corresponded to a given 3D study). Quad-screen display was used to view the 2D parasternal long-axis and short-axis views and apical 4-chamber, 2-chamber, and long-axis views at baseline ( Video 1 ). The baseline 3D echocardiographic data set was first correctly aligned to visualize the true LV apex and then automatically sliced in 3 apical and 9 equidistant 2D short-axis planes orthogonal to the z -axis of the original data sets ( Figure 2 , Video 2 ). When needed, x -axis and y -axis fine rotation was performed to ensure that these short-axis planes were perpendicular to the true LV long-axis dimension.
Wall motion at peak stress and during recovery was assessed using a side-by-side visual assessment of the same electrocardiographically gated 2D view ( Video 3 ) and 3D echocardiographic plane from each of the 3 stages of DipSE visualized in quad-screen display ( Figure 3 , Videos 4 a and 4b). A normal response to DipSE was defined as increased wall motion or increased wall thickening during stress. The development of new or worsening resting LV wall motion abnormalities in >1 contiguous segment of the same vascular territory was considered a sign of inducible ischemia. Segmental wall motion was scored as follows: 1 = normal or hyperkinetic, 2 = hypokinetic, 3 = akinetic, and 4 = dyskinetic. A global wall motion score index was derived by dividing the sum of individual visualized segment scores by the number of visualized segments. To compare 2D echocardiography (2DE) and 3DE in the evaluation of the apex, the regional wall motion score of the 5 apical segments was calculated. Segments with resting wall motion abnormalities that did not show any change during dipyridamole infusion were defined as scar. Akinetic segments that became dyskinetic were not considered indicative of myocardial ischemia.
Coronary angiograms were obtained in 44 patients within 1 month (10 ± 9 days) without any intervening event, on the basis of the recommendations of the referring physician. Luminal narrowing > 50% was considered significant.
Intraobserver and Interobserver Agreement
To assess the reproducibility of wall motion analysis on 3DE and 2DE, the data sets of 10 random patients were reanalyzed by the same observer (L.P.B.) 3 months after the first assessment, as well as by a second observer (F.R.) blinded to the results of the first observer. Concordance rates (normal vs abnormal) were calculated on a patient basis and a coronary perfusion territory basis.
Data are expressed as mean ± SD. Student’s t test was used for comparisons of continuous variables. Agreement between the test results obtained using 2DE and 3DE was tested by measuring the coefficient of variation (κ). A κ value ≥ 0.45 was considered to indicate good agreement, and a κ value ≥ 0.75 was considered to indicate excellent agreement. Sensitivity, specificity, and accuracy were calculated in patients who underwent coronary angiography. A P value < .05 was considered statistically significant.
Demographic and clinical characteristics of the 107 study patients are listed in Table 1 . Because at the time this study was performed, the 3D LV opacification modality was not optimized on the E9 scanner, 17 patients with suboptimal image quality requiring contrast infusion on 2DE were excluded. Another 6 patients in whom, despite adequate 2D images, the endocardium was not adequately visualized on 3DE in >3 segments were also excluded. Therefore, the overall feasibility of 3DE with DipSE in our study patients was 79%.
|Age (y)||68 ± 13|
|Noncardiac surgery preoperative assessment||63 (59%)|
|Angina pectoris (unable to exercise)||44 (41%)|
|Myocardial infarction||25 (23%)|
|Previous PCI||13 (12%)|
|Previous CABG||8 (8%)|
Both 2D and 3D echocardiographic acquisitions were successfully completed in the remaining 84 patients. The average acquisition time for all necessary views to assess all 17 segments was longer using 2DE than 3DE (65 ± 30 vs 16 ± 3 seconds, respectively; P < .0001). Analysis time of 2D cine loops (mean, 176 ± 63 seconds; range, 145-300 seconds) was also significantly longer than that of 3D echocardiographic data sets (mean, 91 ± 5 seconds; range, 80-135 seconds) ( P < .0001). As expected, temporal resolution was significantly higher using 2DE than 3DE (75 ± 5 frames/s vs 41 ± 5 volumes/s, respectively; P < .0001). Using the midsize volume setting, the entire LV volume was fully encompassed in the 3D data set in 78 of the 84 patients (average temporal resolution, 46 ± 3 volumes/s). In the remaining 6 patients, the large-size volume was used (average temporal resolution, 27 ± 2 volumes/s).
A total of 1428 segments were analyzed both at baseline and during peak dipyridamole infusion ( Table 2 ). The number of uninterpretable segments was significantly higher with 2DE than with 3DE at baseline ( Table 2 ), and they were located mainly in the anterior and lateral walls with both modalities ( Figure 4 ). However, apical segments were adequately visualized significantly more often with 3DE than with 2DE both at baseline and during peak stress ( Figure 4 ). During peak stress, the number of uninterpretable segments decreased significantly with both modalities and was no longer different between them ( Table 2 ).
|Adequate 3D echocardiographic imaging||84 (79%)|
|Heart rate (beats/min)|
|Baseline||79 ± 13|
|Peak stress||115 ± 15|
|Blood pressure (mm Hg)|
|Baseline||131 ± 16|
|Peak stress||125 ± 34|
|Reason for test termination|
|End of the protocol||46 (55%)|
|New or worsening wall motion||38 (45%)|
|LV segments available for analysis||1428 × 2|
|Uninterpretable segments on 2DE||311|
|Peak stress||114 (8%)|
|Uninterpretable segments on 3DE||213 ( P < .001 vs 2DE)|
|Baseline||127 (9%) ( P < .03 vs 2DE)|
|Peak stress||81 (6%)|