ABSTRACT: Remarkable advancements have taken place in echocardiography over the last decade. Real-time 3-dimensional echocardiography (RT3DE) has had an impact on numerous clinical applications, from chamber quantification to percutaneous and intraoperative procedural guidance. Novel techniques are emerging to assess left ventricular (LV) dyssynchrony. Contrast agents have undergone recent labeling changes and reestablished their roles in clinical echocardiography. Intracardiac echocardiography continues to have a role in interventional guidance with improved capabilities. The ultrasound machines and transducers continue to become more miniaturized and portable. This review summarizes recent developments in echocardiography, with current clinical applications, limitations and future directions.
Key words: real-time three dimensional echocardiography; stress echocardiography; valvular heart disease
J INVASIVE CARDIOL 2009;21:346–351
Real-Time Three-Dimensional Echocardiography
Earlier efforts in three-dimensional (3-D) echocardiography involved the sequential acquisition of two-dimensional (2-D) images and offline reconstruction of 3-D images. Both the difficult acquisition and lengthy post processing hampered clinical utility. Recently, transducers, electronic technology and post-processing speed have improved to allow a direct, volumetric acquisition of 3-D pyramidal data and real-time display. The matrix-array transducer contains approximately 3,000 imaging elements, compared to 64–80 elements in the phase-array transducer, and has been miniaturized to fit into an X7-2t transesophageal (TEE) probe (Philips Medical Systems, Andover, Massachusetts) as well as a transthoracic (TTE) probe (available from all major vendors). The pyramidal data can be rotated in any arbitrary plane and cropped to show a structure of interest in detail. The ease and speed of image manipulation resemble those of volume-rendered images acquired from multidetector computed tomography (MDCT), but are coupled with the advantage of real-time visualization. Small volumes can be acquired in a single heart beat and displayed instantaneously, making it suitable for interventional guidance and interrogation of valves, interatrial septum and intracardiac mass. Full-volume scans of the entire heart may require smaller subvolumes acquired over 4–7 cardiac cycles with respiratory and electrocardiographic (ECG) gating and remain near real-time. Single-beat full-volume imaging has recently been introduced, but requires validation. Simultaneous biplane display is also possible to reduce scan time.
Chamber volume, function and mass quantification.
Left ventricle. The left ventricular (LV) chamber volume, mass and ejection fraction (EF) measurements by real-time 3--dimensional echocardiography (RT3DE) have been validated against magnetic resonance imaging (MRI) measurements.1–3 The modified Simpson’s method is currently the method of choice for the 2-D quantification of LV volume and EF. It is based on the summation of a stack of elliptical (biplane method) or circular (single-plane method) discs. Foreshortening can further reduce accuracy and reproducibility. The 3-D method can utilize direct volumetric measurement based on semiautomatic endocardial border detection (Figure 1). This method obviates the need for geometric assumption and is independent of foreshortening. It has shown a good correlation with MRI measurements and improved reproducibility compared with 2-D methods, making it more suitable for serial follow up.4
Right ventricle. The independence from geometric assumptions is particularly important for right ventricular (RV) chamber quantification due to its complex crescent shape. The RV chamber volume and EF by RT3DE correlated well with MRI measurements and were more reproducible than 2-D-based measurements.5,6 However, 3DRTE analyses in these studies required significant operator input to define endocardial border and/or specialized software for post processing.
Atria. The left and right atrial volumes obtained by the volumetric RT3DE method have correlated well with the 2-D-based methods.7,8 The RT3DE method employs a semiautomatic contour tracing of left atrium after manual making of five atrial reference points on 2-D images. This method was more sensitive to left atrial volume changes than 2-D-based methods, owing to the freedom from geometric assumptions.8 A recent study showed a good correlation between the RT3DE LA volumes with MRI measurements.9 As the left atrial size and function are associated with various cardiovascular diseases, accuracy and reproducibility are critical. Recently, the RT3DE method has also shown a significant decrease in left atrial volume in patients who maintained sinus rhythm 3 months after atrial fibrillation ablation compared with patients who had recurrence.10
Valves. RT3DE offers unique, realistic anatomic views of valves (Figure 2). Real-time, single-beat acquisition is particularly useful for small-volume structures such as valves. Coupled with the superior image quality of TEE, RT3DE TEE renders exquisite details of both native and prosthetic mitral valves as well as annuloplasty rings: scallops, flail or prolapsed segments, ring dehiscence, struts and prosthetic leaflet malfunction.11–13 Optimal visualization is less for aortic and tricuspid valves, in part due to their anterior location.
In addition to anatomic details, RT3DE has enhanced the understanding of regurgitant mechanism and hemodynamics. Veronesi et al noted a difference in the dynamic changes in mitral annular area, motion and papillary muscle displacement in patients with ischemic or dilated cardiomyopathy.14 The latter group had larger and less variable annular area, along with better-preserved papillary muscle symmetry. Other studies employed direct 3-D color Doppler measurements to reveal limitations of current 2-D-based quantifications. Vena contracta width and proximal isovelocity surface area (PISA) are used to quantify regurgitation jets, and assumed to be circular or hemispheric, respectively. The 3-D color Doppler measurements revealed a significant asymmetry in vena contracta area and PISA in patients with mitral valve prolapse and functional mitral regurgitation.15 Another study also showed significant asymmetry in vena contracta area, especially in eccentric and significant mitral regurgitation.16 Plicht et al showed in an in-vitro study that the true aortic regurgitant orifice area for noncircular orifice shape correlated better with a 3-D color Doppler measurement than a 2-D-based method.17 The current limitations of 3-D color Doppler include multibeat acquisition over 7–10 cardiac cycles, limited sector angle and low spatial resolution of gray-scale images when acquired simultaneously with color. Single-beat acquisition has been recently introduced. Further improvements in spatial and temporal resolution of 3-D color Doppler would enable better quantification of valvular regurgitation and impact future repair design.
Guidance during percutaneous interventions. RT3DE volumetric, real-time acquisition facilitates the monitoring of catheters, wires and devices. Constant adjustments essential during 2-D studies are no longer necessary. Multiple studies have shown the practical utility and incremental value of RT3DE during percutaneous device deployments for patent foramen ovale,18 atrial septal defects,19–21 ventricular septal defects,22,23 mitral paravalvular leak24,25 and left atrial appendage26 (Figures 3 and 4). In particular, RT3DE TEE’s en-face views of atrial septal defect have revealed the pitfall of 2-D TEE or intracardiac echocardiographic (ICE) measurements in potentially misrepresenting true maximum and minimum diameters of noncircular defects.21 RT3DE TEE renders direct, dynamic visualization of septal defects: the location and relationship with adjacent structures; irregular shape and size of the defect; rim competency and size; and the presence of fenestration and/or interatrial septal aneurysm. These characteristics are important in determining the feasibility and execution of percutaneous closure devices (Figures 5 and 6).
RT3DE is also useful during percutaneous balloon mitral valvuloplasty for calcific mitral stenosis. The pressure half-time method has been shown to inaccurately assess mitral valve area immediately post procedure. RT3DE offers en-face views of the smallest orifice near the annulus during diastole. When compared to the pressure half-time method, the planimetry of this area correlated better with the mitral valve area obtained by the continuity equation.27
Intracardiac mass. RT3DE has been shown to add incremental values to diagnosing intracardiac tumor and thrombi.28–30 Sites of attachment, spatial relationships with adjacent structures and exquisite anatomic details of masses can be displayed dynamically. While cine MRI studies may offer similar information, RT3DE images are not restricted preplanned imaging planes and can be rotated in real time to aid surgical planning.
Detection of ischemia. The volumetric data of RT3DE provide multislice 2-D images from base to apex. The full-volume data can be acquired from one apical transducer location and the scan time can be less than 4 seconds with a newer transducer.31 This rapid acquisition could potentially improve sensitivity for diagnosis and prognosis of coronary artery disease. The extraction of multislice 2-D images from full-volume images also avoids misalignment or foreshortening that is possible in a 2-D stress echocardiography (Figure 7).
Studies have shown the feasibility of RT3DE during treadmill and dobutamine stress tests compared with traditional 2-D methods and the exercise thallium single-photon emission computed tomographic test.31–33 Concordance has been variable ranging between 69–89%.31–35 One limitation of RT3DE stress tests in these studies is its temporal resolution (less than 20 Hz). Also, multiple sub-volume data are combined to generate a full volume, which is then subject to cardiac and respiratory motion, arrhythmia and stitch artifacts. Patients with arrhythmia were excluded in these studies due to the obligatory ECG-gated multibeat acquisition during a breathhold. Single-beat full-volume acquisition has become available to address these limitations, but no validation study exists at the time of this review.
Cardiac resynchronization therapy (CRT). Tissue Doppler imaging (TDI) has been the standard method in 2-D echocardiography to measure mechanical dyssynchrony.36 TDI assesses regional myocardial velocities, strain and strain rate. However, the signal-to-noise ratio and angle dependency have limited the reproducibility and clinical utility of TDI-based measurements of dyssynchrony in large trials.37,38 RT3DE allows measurement of segmental systolic contraction timing, known as Systolic Dyssynchrony Index (SDI). The 3-D LV volume is divided into sixteen segments. All segments in a normal heart would achieve minimal volume simultaneously in end systole. Mechanical dyssynchrony is represented by the temporal dispersion of segmental systolic contraction timing. The SDI is a standard deviation of time to minimum systolic volume per segment, normalized by a R-R interval (Figure 8). A recent study showed that the SDI predicted improvement in LV function 6 months after CRT.39 In another study, those with a higher SDI had a greater LV end-systolic volume reduction after CRT.40 Because the SDI is based on a full-volume acquisition, the SDI is subject to the limitations of multi-beat acquisitions mentioned earlier. Temporal resolution is also significantly lower than TDI-based methods. Larger studies are needed to establish cut-off values of SDI to define dyssynchrony.
Speckle Tracking
CRT has been shown to improve survival in patients with advanced heart failure. However, patient selection for clinical response to CRT remains a challenge. A recent, multicenter, prospective trial has shown no single echocardiographic measure of dyssynchrony among conventional 2-D and tissue Doppler-based methods to improve patient selection for CRT, owing to challenging signal-to-noise ratio, angle dependency and resultant low reproducibility.37 This trial has been criticized for site selection bias, variable equipment quality and inadequate training for acquisition and analysis.41 Currently, the guidelines do not recommend using echocardiographic Doppler dyssynchrony studies to withhold CRT for those who meet accepted criteria.36
Speckle-tracking-based imaging is a non-Doppler-based approach and tracks the motion of each speckle formed by acoustic backscatter generated by myocardial tissue-ultrasound interaction and representing myocardial motion. Speckle-tracking based measurements are angle-independent and have shown better reproducibility than Doppler-based strain and strain-rate imaging.42 One study showed that a combination of speckle-tracking and TDI measurements improved CRT response prediction.43 Speckle-tracking-based radial strain was complementary to TDI-based longitudinal strain in increasing the sensitivity and specificity for predicting CRT response than each technique separately. However, temporal resolution of speckle tracking remains lower than TDI methods (50–70 fps vs. > 130 fps) and may result in possible undersampling of data.
Contrast Echocardiography
Current FDA-approved clinical indications of echocardiographic contrast agents are LV opacification and endocardial border definition in patients with two or more suboptimally visualized segments. Two agents are currently available in the U.S.: Definity (Lantheus Medical Imaging, North Billerica, Massachusetts) and Optison (GE Healthcare, Buckinghamshire, United Kingdom). They are perfluorocarbon-containing microbubbles coated with lipid or protein and are injected intravenously. Studies have shown that the use of contrast agents improves the diagnostic accuracy of LV function quantification,44,45 regional wall motion,46,47 detection of LV thrombus,48 apical aneurysm and intracardiac mass.49 No contrast agent is currently approved for myocardial perfusion application, though one agent is seeking FDA approval (Imagify, Acusphere, Watertown, Massachusetts).
In October 2007, the black box warning contraindicated the use of perflutren-containing contrast agents in patients with a number of conditions including acute coronary syndrome or unstable heart failure. A 30-minute monitoring was required after each injection. The warning followed four postmarketing deaths that were temporally related to the use of contrast agents. Subsequently, a number of studies have shown data consistent with the efficacy and safety of agents.50,51 One multicenter, retrospective study examined over 78,000 doses of the contrast agents, including over 10,000 doses given to critically ill patients.52 Severe reactions were present in 0.01%, including 0.006% of anaphylactic reactions. No deaths were reported. In May and June 2008, the FDA revised the warning to remove all contraindications except hypersensitivities to perflutren and right-to-left, bidirectional or transient right-to-left cardiac shunts. The 30-minute monitoring is now limited to patients with pulmonary hypertension or unstable cardiopulmonary conditions.
Intracardiac Echocardiography
The currently available phased-array ICE catheters offer a deflectable tip, up to 12 cm in depth, as well as spectral, color and tissue Doppler capabilities (Acuson AcuNav, Siemens Medical Solutions). They are used to guide transseptal punctures and catheter ablation for atrial and ventricular tachyarrhythmia. Several studies have shown the feasibility of a 3-D reconstruction of the left atrium and pulmonary veins with an ICE catheter located in the right atrium.53,54 The new CartoSound system (Biosense Webster, Diamond Bar, California) contains an ICE catheter with an electroanatomic location sensor (Soundstar, Biosense Webster). 3-D volume was reconstructed from the endocardial tracings obtained from sequential 2-D planar images. Real-time 3-D volume-rendered images resulted in improved registration with electroanatomic mapping compared to MDCT images.53 The application supports better efficacy and safety of ablation procedures, and avoids misregistration issues of MDCT or MRI images acquired during different respiratory and cardiac phases and loading condition. However, much like earlier efforts of 3-D echocardiography prior to the advent of matrix-array transducer and improved processing, the current process remains subject to lengthy reconstruction. Similar effort has been made to reconstruct 3-D volume of the LV during ventricular tachycardia ablation.55 Recent developments similar to RT3DE technology seem promising, but also raise the concerns of cost and availability of single-use catheters.
Hand-Held Echocardiography
Currently, the smallest hand-held cardiac scanner weighs 1.6 pounds and has 2-D gray-scale capability only (Acuson P10, Siemens Medical Solutions, Mountain View, California). The clinical cardiac application is a screening or focused evaluation mainly of LV size and function, wall motion abnormalities and pericardial effusion to serve as a triage tool or extension of physical examination. Studies have shown acceptable levels of accuracy and reliability for focused evaluations.56–58 Quality assurance of the operator regarding acquisition and interpretation remains an issue. Current recommendations include 150 performed examinations.59
Recently, multimodality ultrasound machines have become more compact and portable. All major vendors now carry a notebook platform attached to a mobile cart and are capable of 2-D, spectral and color Doppler imaging and, in many, TDI as well. Some, weighing less than 12 pounds, are equipped with a 2-D TEE or ICE capabilities.
Conclusion
The inherent strengths of echocardiography are safety, portability and comprehensive anatomic and hemodynamic information. Recent developments in RT3DE have increased the accuracy and reproducibility in chamber quantification and overcome the 2-D limitations of geometric assumptions. In valvular diseases, it offers unprecedented anatomic and hemodynamic information, especially for the mitral valve. Its utility in procedural guidance is multifaceted in interventional and operating suites from accurate preprocedural planning and efficient intraprocedural monitoring. 3-D color Doppler promises to offer accurate volumetric quantification of regurgitant lesions, shunts and cardiac output. Further improvement in temporal and spatial resolution of RT3DE will increase its role in stress echocardiography and CRT. Speckle-tracking is another alternative to address the current limitations of TDI in cardiac resynchronization therapy. Contrast echocardiography has reestablished its clinical role after recent labeling changes. ICE is expanding its role in interventional guidance, with added capabilities where available. The miniaturization trend continues, now from a pocket-sized machine for focused exams to a multimodality notebook platform.
From the Division of Cardiology, Harbor UCLA Medical Center, Torrance, California.
The author reports no conflicts of interest regarding the content herein.
Manuscript submitted May 4, 2009 and accepted May 11, 2009.
Address for correspondence: Jina Chung, MD, FACC, Medicine; Director, Echo Lab; Assistant Director, Cardiac CT, Harbor UCLA Medical Center, 1000 West Carson Street, Box 405, Torrance, CA 90509. E-mail: jinachung@labiomed.org
1. Mor-Avi V, Jenkins C, Kuhl HP, et al. Real-time 3-dimensional echocardiographic quantification of left ventricular volumes: Multicenter study for validation with magnetic resonance imaging and investigation of sources of error. JACC Cardiovasc Imaging 2008;1:413–423.
2. Mor-Avi V, Sugeng L, Weinert L, et al. Fast measurement of left ventricular mass with real-time three-dimensional echocardiography: Comparison with magnetic resonance imaging. Circulation 2004;110:1814–1818.
3. Pouleur AC, le Polain de Waroux JB, et al. Assessment of left ventricular mass and volumes by three-dimensional echocardiography in patients with or without wall motion abnormalities: Comparison against cine magnetic resonance imaging. Heart 2008;94:1050–1057.
4. Jenkins C, Bricknell K, Chan J, et al. Comparison of two- and three-dimensional echocardiography with sequential magnetic resonance imaging for evaluating left ventricular volume and ejection fraction over time in patients with healed myocardial infarction. Am J Cardiol 2007;99:300–306.
5. Niemann PS, Pinho L, Balbach T, et al. Anatomically oriented right ventricular volume measurements with dynamic three-dimensional echocardiography validated by 3-Tesla magnetic resonance imaging. J Am Coll Cardiol 2007;50:1668–1676.
6. Jenkins C, Chan J, Bricknell K, et al. Reproducibility of right ventricular volumes and ejection fraction using real-time three-dimensional echocardiography: Comparison with cardiac MRI. Chest 2007;131:1844–1851.
7. Muller H, Burri H, Lerch R. Evaluation of right atrial size in patients with atrial arrhythmias: Comparison of 2-D versus real time 3-D echocardiography. Echocardiography 2008;25:617–623.
8. Anwar AM, Soliman OI, Geleijnse ML, et al. Assessment of left atrial volume and function by real-time three-dimensional echocardiography. Int J Cardiol 2008;123:155–161.
9. Artang R, Migrino RQ, Harmann L, et al. Left atrial volume measurement with automated border detection by 3-dimensional echocardiography: Comparison with magnetic resonance imaging. Cardiovasc Ultrasound 2009;7:16.
10. Marsan NA, Bleeker GB, van Bommel RJ, et al. Comparison of time course of response to cardiac resynchronization therapy in patients with ischemic versus nonischemic cardiomyopathy. Am J Cardiol 2009;103:690–694.
11. Sugeng L, Shernan SK, Weinert L, et al. Real-time three-dimensional transesophageal echocardiography in valve disease: Comparison with surgical findings and evaluation of prosthetic valves. J Am Soc Echocardiogr 2008;21:1347–1354.
12. Sugeng L, Shernan SK, Salgo IS, et al. Live 3-dimensional transesophageal echocardiography initial experience using the fully-sampled matrix array probe. J Am Coll Cardiol 2008;52:446–449.
13. Grewal J, Mankad S, Freeman WK, et al. Real-time three-dimensional transesophageal echocardiography in the intraoperative assessment of mitral valve disease. J Am Soc Echocardiogr 2009;22:34–41.
14. Veronesi F, Corsi C, Sugeng L, et al. Quantification of mitral apparatus dynamics in functional and ischemic mitral regurgitation using real-time 3-dimensional echocardiography. J Am Soc Echocardiogr 2008;21:347–354.
15. Kahlert P, Plicht B, Schenk IM, et al. Direct assessment of size and shape of noncircular vena contracta area in functional versus organic mitral regurgitation using real-time three-dimensional echocardiography. J Am Soc Echocardiogr 2008;21:912–921.
16. Little SH, Pirat B, Kumar R, et al. Three-dimensional color Doppler echocardiography for direct measurement of vena contracta area in mitral regurgitation: In vitro validation and clinical experience. JACC Cardiovasc Imaging 2008;1:695–704.
17. Plicht B, Kahlert P, Goldwasser R, et al. Direct quantification of mitral regurgitant flow volume by real-time three-dimensional echocardiography using dealiasing of color Doppler flow at the vena contracta. J Am Soc Echocardiogr 2008;21:1337–1346.
18. Martin-Reyes R, Lopez-Fernandez T, Moreno-Yanguela M, et al. Role of real-time three-dimensional transoesophageal echocardiography for guiding transcatheter patent foramen ovale closure. Eur J Echocardiogr 2009;10:148–150.
19. Ben Zekry S, Guthikonda S, Little SH, et al. Percutaneous closure of atrial septal defect. JACC Cardiovasc Imaging 2008;1:515–517.
20. Bhan A, Kapetanakis S, Pearson P, et al. Percutaneous closure of an atrial septal defect guided by live three-dimensional transesophageal echocardiography. J Am Soc Echocardiogr 2009.
21. Lodato JA, Cao QL, Weinert L, et al. Feasibility of real-time three-dimensional transoesophageal echocardiography for guidance of percutaneous atrial septal defect closure. Eur J Echocardiogr 2009;22:753.
22. Halpern DG, Perk G, Ruiz C, et al. Percutaneous closure of a post-myocardial infarction ventricular septal defect guided by real-time three-dimensional echocardiography. Eur J Echocardiogr 2009;10:569–571.
23. Acar P, Abadir S, Aggoun Y. Transcatheter closure of perimembranous ventricular septal defects with Amplatzer occluder assessed by real-time three-dimensional echocardiography. Eur J Echocardiogr 2007;8:110–115.
24. Biner S, Rafique AM, Kar S, Siegel RJ. Live three-dimensional transesophageal echocardiography-guided transcatheter closure of a mitral paraprosthetic leak by Amplatzer occluder. J Am Soc Echocardiogr 2008;21:1282 e7–e9.
25. Bavikati VV, Babaliaros VC, Lerakis S. Utility of three-dimensional echocardiography in percutaneous closure of paravalvular leak. Echocardiography 2008 Nov 11. [Epub ahead of print]
26. Uretsky S, Shah A, Bangalore S, et al. Assessment of left atrial appendage function with transthoracic tissue Doppler echocardiography. Eur J Echocardiogr 2009;10:363–371.
27. Chu JW, Levine RA, Chua S, et al. Assessing mitral valve area and orifice geometry in calcific mitral stenosis: A new solution by real-time three-dimensional echocardiography. J Am Soc Echocardiogr 2008;21:1006–1009.
28. Lo CI, Chang SH, Hung CL. Demonstration of left ventricular thrombi with real-time 3-dimensional echocardiography in a patient with cardiomyopathy. J Am Soc Echocardiogr 2007;20:905.
29. Yang HS, Arabia FA, Chaliki HP, et al. Images in cardiovascular medicine. Left atrial fibroma in gardner syndrome: Real-time 3-dimensional transesophageal echo imaging. Circulation 2008;118:e692–e696.
30. Chamsi-Pasha MA, Anwar AM, Nosir YF, et al. Right atrial myxoma associated with an atrial septal defect by real-time three-dimensional echocardiography. Eur J Echocardiogr 2009;10:362–364.
31. Yang HS, Pellikka PA, McCully RB, et al. Role of biplane and biplane echocardiographically guided 3-dimensional echocardiography during dobutamine stress echocardiography. J Am Soc Echocardiogr 2006;19:1136–1143.
32. Matsumura Y, Hozumi T, Arai K, et al. Non-invasive assessment of myocardial ischaemia using new real-time three-dimensional dobutamine stress echocardiography: Comparison with conventional two-dimensional methods. Eur Heart J 2005;26:1625–1632.
33. Zwas DR, Takuma S, Mullis-Jansson S, et al. Feasibility of real-time 3-dimensional treadmill stress echocardiography. J Am Soc Echocardiogr 1999;12:285–289.
34. Takeuchi M, Otani S, Weinert L, et al. Comparison of contrast-enhanced real-time live 3-dimensional dobutamine stress echocardiography with contrast 2-dimensional echocardiography for detecting stress-induced wall-motion abnormalities. J Am Soc Echocardiogr 2006;19:294–299.
35. Ahmad M, Xie T, McCulloch M, et al. Real-time three-dimensional dobutamine stress echocardiography in assessment stress echocardiography in assessment of ischemia: Comparison with two-dimensional dobutamine stress echocardiography. J Am Coll Cardiol 2001;37:1303–1309.
36. Gorcsan J 3rd, Abraham T, Agler DA, et al. Echocardiography for cardiac resynchronization therapy: Recommendations for performance and reporting — A report from the American Society of Echocardiography Dyssynchrony Writing Group endorsed by the Heart Rhythm Society. J Am Soc Echocardiogr 2008;21:191–213.
37. Chung ES, Leon AR, Tavazzi L, et al. Results of the predictors of response to CRT (PROSPECT) trial. Circulation 2008;117:2608–2616.
38. Beshai JF, Grimm RA, Nagueh SF, et al. Cardiac-resynchronization therapy in heart failure with narrow QRS complexes. N Engl J Med 2007;357:2461–471.
39. Marsan NA, Bleeker GB, Ypenburg C, et al. Real-time three-dimensional echocardiography permits quantification of left ventricular mechanical dyssynchrony and predicts acute response to cardiac resynchronization therapy. J Cardiovasc Electrophysiol 2008;19:392–399.
40. Soliman OI, van Dalen BM, Nemes A, et al. Quantification of left ventricular systolic dyssynchrony by real-time three-dimensional echocardiography. J Am Soc Echocardiogr 2009;22:232–239.
41. Yu CM, Bax JJ, Gorcsan J 3rd. Critical appraisal of methods to assess mechanical dyssynchrony. Curr Opin Cardiol 2009;24:18–28.
42. Gorcsan J 3rd, Tanabe M, Bleeker GB, et al. Combined longitudinal and radial dyssynchrony predicts ventricular response after resynchronization therapy. J Am Coll Cardiol 2007;50:1476–1483.
43. Hanekom L, Cho GY, Leano R, et al. Comparison of two-dimensional speckle and tissue Doppler strain measurement during dobutamine stress echocardiography: An angiographic correlation. Eur Heart J 2007;28:1765–1772.
44. Yu EH, Sloggett CE, Iwanochko RM, et al. Feasibility and accuracy of left ventricular volumes and ejection fraction determination by fundamental, tissue harmonic, and intravenous contrast imaging in difficult-to-image patients. J Am Soc Echocardiogr 2000;13:216–224.
45. Hundley WG, Kizilbash AM, Afridi I, et al. Administration of an intravenous perfluorocarbon contrast agent improves echocardiographic determination of left ventricular volumes and ejection fraction: Comparison with cine magnetic resonance imaging. J Am Coll Cardiol 1998;32:1426–1432.
46. Plana JC, Mikati IA, Dokainish H, et al. A randomized cross-over study for evaluation of the effect of image optimization with contrast on the diagnostic accuracy of dobutamine echocardiography in coronary artery disease. The OPTIMIZE Trial. JACC Cardiovasc Imaging 2008;1:145–152.
47. Dolan MS, Riad K, El-Shafei A, et al. Effect of intravenous contrast for left ventricular opacification and border definition on sensitivity and specificity of dobutamine stress echocardiography compared with coronary angiography in technically difficult patients. Am Heart J 2001;142:908–915.
48. Thanigaraj S, Schechtman KB, Perez JE. Improved echocardiographic delineation of left ventricular thrombus with the use of intravenous second-generation contrast image enhancement. J Am Soc Echocardiogr 1999;12:1022–1026.
49. Kirkpatrick JN, Wong T, Bednarz JE, et al. Differential diagnosis of cardiac masses using contrast echocardiographic perfusion imaging. J Am Coll Cardiol 2004;43:1412–1419.
50. Main ML, Goldman JH, Grayburn PA. Thinking outside the “box” — The ultrasound contrast controversy. J Am Coll Cardiol 2007;50:2434–2437.
51. Herzog CA. Incidence of adverse events associated with use of perflutren contrast agents for echocardiography. JAMA 2008;299:2023–2025.
52. Wei K, Mulvagh SL, Carson L, et al. The safety of deFinity and Optison for ultrasound image enhancement: A retrospective analysis of 78,383 administered contrast doses. J Am Soc Echocardiogr 2008;21:1202–1206.
53. den Uijl DW, Tops LF, Tolosana JM, et al. Real-time integration of intracardiac echocardiography and multislice computed tomography to guide radiofrequency catheter ablation for atrial fibrillation. Heart Rhythm 2008;5:1403–1410.
54. Packer DL, Johnson SB, Kolasa MW, et al. New generation of electro-anatomic mapping: Full intracardiac ultrasound image integration. Europace 2008;10(Suppl 3):iii35–iii41.
55. Khaykin Y, Skanes A, Whaley B, et al. Real-time integration of 2-D intracardiac echocardiography and 3-D electroanatomical mapping to guide ventricular tachycardia ablation. Heart Rhythm 2008;5:1396–1402.
56. Manasia AR, Nagaraj HM, Kodali RB, et al. Feasibility and potential clinical utility of goal-directed transthoracic echocardiography performed by noncardiologist intensivists using a small hand-carried device (SonoHeart) in critically ill patients. J Cardiothorac Vasc Anesth 2005;19:155–159.
57. Egan M, Ionescu A. The pocket echocardiograph: A useful new tool? Eur J Echocardiogr 2008;9:721–725.
58. Spurney CF, Sable CA, Berger JT, Martin GR. Use of a hand-carried ultrasound device by critical care physicians for the diagnosis of pericardial effusions, decreased cardiac function, and left ventricular enlargement in pediatric patients. J Am Soc Echocardiogr 2005;18:313–319.
59. Seward JB, Douglas PS, Erbel R, et al. Hand-carried cardiac ultrasound (HCU) device: Recommendations regarding new technology. A report from the Echocardiography Task Force on New Technology of the Nomenclature and Standards Committee of the American Society of Echocardiography. J Am Soc Echocardiogr 2002;15:369–373.
60. Hung J, Lang R, Flachskampf F, et al. 3-D echocardiography: A review of the current status and future directions. J Am Soc Echocardiogr 2007;20:213–233.
61. Schwalm SA, Sugeng L, Raman J, et al. Assessment of mitral valve leaflet perforation as a result of infective endocarditis by 3-dimensional real-time echocardiography. J Am Soc Echocardiogr 2004;17:919–922.
62. Shah SJ, Bardo DM, Sugeng L, et al. Real-time three-dimensional transesophageal echocardiography of the left atrial appendage: Initial experience in the clinical setting. J Am Soc Echocardiogr. 2008;21:1362–1368.
63. Lang RM, Mor-Avi V, Sugeng L, et al Three-dimensional echocardiography: The benefits of the additional dimension. J Am Coll Cardiol 2006;48:2053–2069.
