Cardiac functional stress imaging: A sequential approach with stress echo and cardiovascular magnetic resonance
© Sicari et al; licensee BioMed Central Ltd. 2007
Received: 26 October 2007
Accepted: 04 December 2007
Published: 04 December 2007
The aim of the study was to assess the feasibility and accuracy of an integrated stress imaging algorithm with echo first and second-line Cardiac Magnetic Resonance (CMR) in selected cases. Stress echo (SE) is widely used for non-invasive diagnosis of coronary artery disease (CAD), but difficult patients and ambiguous responses may be met even with top-level technology and expertise. CMR might ideally complement SE in well-selected cases with unfeasible and/or ambiguous and/or submaximal results.
Methods and results
152 in-hospital patients with chest pain and normal baseline function were referred for SE and coronary angiography. Of the initial population, 33 were shunted to CMR due to poor acoustic window or ambiguous or submaximal SE test. The only criterion of positivity for both techniques was the presence of regional wall motion abnormalities in at least 2 contiguous segments. Coronary angiography was performed independently of test results. Significant CAD was identified by a >50% quantitatively assessed diameter reduction in at least 1 major coronary vessel.
CAD was present in 88 patients. Interpretable and diagnostic stress test were obtained in 143 patients with the sequential algorithm. The sequential (SE in 110 + CMR in 33 patients) algorithm showed a sensitivity of 76% (95% CI 66% to 85%) specificity of 87% (95% CI 76% to 95%) and accuracy of 80% (95% CI 73% to 86%).
A sequential functional stress imaging algorithm with stress echo first and stress CMR in selected cases is feasible, clinically realistic and allows an efficient, radiation-free diagnosis of CAD.
Stress echocardiography is an established cost-effective technique for the detection of coronary artery disease . According to the guidelines of European Society of Cardiology and American Society of Echocardiography – stress echocardiography (with exercise, dobutamine or dipyridamole) is a class I indication (of documented effectiveness and usefulness) for the diagnosis of coronary artery disease and for the prognostic stratification of patients with known coronary artery disease [2, 3]. The widespread use in the clinical practice has become possible only after evidence collected through large scale multicenter studies that demonstrated its feasibility, safety, diagnostic and prognostic accuracy [4–9]. Its major limitation is related to a high inter-observer variability and to operator-dependent expertise that might be overcome by an appropriate training and the use of strict reading criteria [10–12]. Moreover, a percentage, although small, of patients is not feasible for echo scanning due to an acoustically hostile window (chronic obstructive pulmonary disease, conformation of the thorax etc.). Cardiac magnetic resonance (CMR) is the latest technique entering the field of cardiac imaging [13–16]. The advantages of the technique are related to its less pronounced operator-independence and the absence of ionising radiation, at the price of higher costs and lower availability when compared with echocardiography. Therefore, CMR might represent a good alternative to stress echocardiography when the latter is not feasible or test result is ambiguous. The aim of the study was to assess the feasibility and accuracy of an integrated algorithm with stress echo first and second-line stress CMR in selected cases.
Two-dimensional echocardiography and 12-lead electrocardiographic (ECG) monitoring were performed in combination with high dose dipyridamole (up to 0.84 mg over 6 min) or with semi-supine exercise ECG in accordance to well established protocols [18–20]. Cardiac magnetic resonance was performed in combination with high dose dipyridamole with the same dose used for stress echo [18, 19]. During the procedure, blood pressure and ECG were recorded each minute.
Two-dimensional echocardiographic monitoring was performed throughout and up to 5 min after the end of peak stress. Two-dimensional images were recorded at baseline and at the end of each step. Regional wall motion analysis was evaluated at baseline and at peak stress with a semiquantitative assessment of a wall motion score index (WMSI), with the 17 segment model of the left ventricle, each segment ranging from 1 = normal/hyperkinetic to 4 = dyskinetic, according to the recommendations of the American Heart Association and American Society of Echocardiography [21, 22]. WMSI was derived by dividing the sum of individual segment scores by the number of interpretable segments . Test positivity was defined as the occurrence of at least one of the following conditions: 1) new dyssynergy in a region with normal rest function (i.e., normokinesia becoming hypokinesia, akinesia or dyskinesia) in at least two adjacent segments. Non-echocardiographic test end-points were the following: peak dipyridamole dose; 85% of target heart rate; achievement of conventional end-points (such as severe chest pain and/or diagnostic ST segment changes). The test was also stopped, in the absence of diagnostic endpoints, for one of the following reasons of constituting a submaximal, non-diagnostic test: intolerable symptoms; limiting asymptomatic side effects, consisting of: a) hypertension (systolic blood pressure >220 mmHg; diastolic blood pressure >120 mmHg); b) hypotension (relative or absolute): >30 mmHg fall of blood pressure; c) supraventricular arrhythmias: supraventricular tachycardia or atrial fibrillation; d) ventricular arrhythmias: ventricular tachycardia; frequent, polymorphous premature ventricular beats.
Magnetic resonance analysis
CMR has been performed on a whole body MR scanner (Signa Cvi, GE, USA), operating at 1.5T by using a dedicated cardiac 8 elements phased-array coil. CMR acquisition has been performed according to a standardized protocol. Cardiac images have been obtained using a breath-hold segmented gradient echo Steady State Free Precession (SSFP) electrocardiographic triggered sequences. The echo time was 1.7 ms; repetition time 4.0 ms; slice thickness 8 mm with no interslice gap; field of view from 320 to 380 mm; data matrix size 256 × 224; phase of field of view 0.75; trigger delay was minimum; and views per segment 8 to 12 according to heart rate; flip angle 45°. Thirty cine frames were obtained for each slice. Three short axes slices, respectively at basal, middle and distal levels and 4-, 2-, and 3-chamber views of the left ventricle (LV), have been used for calculating regional wall motion (WM). The basal middle and distal segments were defined in relation to the papillary muscles; basal segments were below and middle segments were above the appearance of papillary muscles; middle segments were in the presence of papillary muscles. The LV has been divided into a 17-segment model. WM has been semi quantitatively assessed as follows: 1 = normokinetic, 2 = hypokinetic, 3 = akinetic and 4 = dyskinetic . A dipyridamole test has been considered to be positive for functional criteria when wall motion worsened in 2 contiguous myocardial segments. There were 2 experienced observers reading wall motion, who were blinded to each other and to angiographic results.
Coronary angiography in multiple views was performed according to the standard Judkins or Sones technique. At least five views (including two orthogonal views) were acquired for the left and at least two orthogonal views for the right coronary arteries, respectively. Additional appropriate projections were obtained in case of superimposition of side branches or foreshortening of the segment of interest. A vessel was considered to have significant obstruction if its diameter was narrowed by 50% with respect to the prestenosic segment. All stenotic segments were evaluated by an automated edge detection system providing the percent stenosis diameter.
Values are expressed as mean ± standard deviation. Proportions were compared by the chi-square statistic; a Fisher's exact test was used when appropriate. A p value <0.05 was considered statistically significant. Calculations of sensitivity, specificity and accuracy were performed according to standard definitions. The 95% CIs were calculated for each technique, and the individual intervals were compared. Differences between techniques were considered significant at the 0.05 level when 95% CI did not overlap.
Clinical characteristics of study population
No. of patients
64 ± 9
History of angina
Patients with CAD
Coronary angiographic results
Coronary angiography demonstrated absence or only non-significant coronary artery disease in 55 patients and significant coronary artery disease in 88: Of these 31 had one vessel disease, 33 two vessel and 24 three vessel disease; left main coronary artery disease was found in 4 patients.
Stress Echocardiography results
Stress echocardiography was diagnostic in 110 patients. Three patients had a poor acoustic window (additional file 1), 1 had an ambiguous response, 29 had a submaximal exercise stress test, and in 4 dipyridamole was prematurely interrupted due to side effects and were referred to dobutamine stress echocardiography (fig. 1). Rest WMSI was 1.0 and peak WMSI was 1.2 ± 0.3. The test was positive in 60 (54.5%) (additional files 2 and 3). Diagnostic ECG changes and chest pain were present during the test in 43 (72%) and 26 (43%) patients of the 60 with a positive test result.
Stress CMR results
The subgroup of 35 patients with a non-diagnostic and/or suboptimal stress echocardiography underwent dipyridamole CMR. The test was feasible in 33 of them (1 did not fit into the MR bore and 1 was not imaged because of anxiety) (fig. 1). Rest WMSI was 1.0 and peak WMSI was 1.12 ± 0.2. The test was positive in 14 (42%) patients (additional files 4 and 5).
Correlation between angiographic data and stress results
Stress CMR can be used to diagnose inducible ischemia in patients unable to undergo stress echocardiography. Diagnostic accuracies of the two techniques are comparable and the more demanding and expensive CMR can be used as a second line technique only when stress echocardiography is submaximal, inconclusive or unfeasible.
In fact, image quality is one of the major limitations of stress echocardiography interpretation and this affects significantly diagnostic accuracy  and wall motion analysis during CMR can overcome this limitation.
Comparison with previous studies
The results of our study are broadly consistent with several studies suggesting that both stress echo (with exercise or pharmacologic stress, both with dipyridamole and dobutamine) and CMR are excellent options for the diagnosis of CAD [23–27]. This has also been stated in recent ESC guidelines  and is in agreement with the recent ESC panel report on the clinical use of CMR that consider stress MR a class II examination for the diagnosis of coronary artery disease . Overall, the feasibility and diagnostic accuracy of each test is lower than previously reported, but this is unavoidable when one moves from initial feasibility studies [15, 26, 29–31] to clinical studies where the technique is deployed in the field on consecutive, challenging and often "difficult" patients . The low sensitivity of the test may be due to several factors: All patients had a normal baseline function; a high number of patients were studied under anti-ischemic therapy (59 out of 152), which reduces sensitivity of wall motion; 31 out of 88 patients had a single vessel disease; Moreover we analysed only regional wall motion for both SE and CMR, without addition of myocardial perfusion or Coronary flow reserve criteria. Nevertheless, the overall performance of the algorithm seemed acceptable in the "real life" context.
Clinical implications: "nobody is perfect"
There are several tests and strategies for the evaluation of patients with known or suspected coronary artery disease, but no single strategy has been demonstrated to be superior overall. The clinical plausibility of this algorithm stems from the obvious fact that "nobody is perfect", also among stress tests, and there is the primary need to optimise economic and technological resources without reducing the standard of diagnostic excellence. In the present study a clinical practical algorithm in which stress echocardiography and stress CMR can be used in a sequential way (see fig.1) for the assessment of CAD is proposed. The 3 major aspects of the algorithm are: 1. restrict the indication to more expensive methods to patients really in need; 2 – to have a maximal result in all patients, since submaximal stress test have low diagnostic and prognostic value [19, 32]; 3 – minimize long term risks due to the use of radiation [33, 34] with a radiation-free stress imaging algorithm allowing to select for coronary angiography and revascularization only patients with a functionally significant, and therefore prognostically malignant, forms of coronary artery disease, who are more likely to benefit from a physiologic driven revascularization. In this algorithm, CMR replaces cardiac stress scintigraphy which gives a dose exposure corresponding to 500 (with Sestamibi) to 1,600 (with Thallium or dual isotope scan) chest x-rays per each exam [33–36]. Since 10 million cardiac stress scintigraphies are performed each year in US, the positive impact of our proposed algorhythm on downstream risks would be remarkable [37, 38]
A sequential functional stress imaging algorithm with stress echo first and stress CMR in selected cases is feasible, clinically realistic and allows a highly efficient, radiation-free diagnosis of CAD in almost all patients in whom cardiac stress imaging is clinically indicated.
Stress CMR is an excellent option when stress echocardiography is inconclusive or unfeasible.
The preliminary data were presented at the European Association of Echocardiography Annual Meeting (Euro Echo), Florence, Italy, December, 2005
Financial support for the present study was received from institutional funding of the CNR, Institute of Clinical Physiology, Pisa, Italy
- Picano E: Stress echocardiography. From pathophysiological toy to diagnostic tool. Circulation. 1992, 85: 1604-1612.View ArticlePubMedGoogle Scholar
- Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F, Daly C, De Backer G, Hjemdahl P, Lopez-Sendon J, Marco J, Morais J, Pepper J, Sechtem U, Simoons M, Thygesen K, Priori SG, Blanc JJ, Budaj A, Camm J, Dean V, Deckers J, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Tamargo J, Zamorano JL: Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology, ESC Committee for Practice Guidelines (CPG). Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology, ESC Committee for Practice Guidelines (CPG). Guidelines on the management of stable angina pectoris: executive summary: the Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. Eur Heart J. 2006, 27: 1341-81.View ArticlePubMedGoogle Scholar
- Pellikka PA, Nagueh SF, Elhendy AA, Elhendy CA, Sawada SG: American Society of Echocardiography recommendations for performance, interpretation, and application of stress echocardiography. J Am Soc Echocardiogr. 2007, 20: 1021-1041.View ArticlePubMedGoogle Scholar
- Picano E, Marini C, Pirelli S, Maffei S, Bolognese L, Chiriatti G, Chiarella F, Orlandini A, Seveso G, Colosso MQ, : Safety of intravenous high-dose dipyridamole echocardiography. Am J Cardiol. 1992, 70: 252-256.View ArticlePubMedGoogle Scholar
- Picano E, Mathias W, Pingitore A, Bigi R, Previtali M, : Safety and tolerability of dobutamine-atropine stress echocardiography: a prospective, large scale, multicenter trial. Lancet. 1994, 344: 1190-1192.View ArticlePubMedGoogle Scholar
- Picano E, Landi P, Bolognese L, Chiaranda G, Chiarella F, Seveso G, Sclavo MG, Gandolfo N, Previtali M, Orlandini A, : Prognostic value of dipyridamole-echocardiography early after uncomplicated myocardial infarction: a large scale multicenter trial. Am J Med. 1993, 11: 608-618. 10.1016/0002-9343(93)90357-U.View ArticleGoogle Scholar
- Sicari R, Pasanisi E, Venneri L, Landi P, Cortigiani L, Picano E: Echo Persantine International Cooperative (EPIC) Study Group; Echo Dobutamine International Cooperative (EDIC) Study Group. Stress echo results predict mortality: a large scale multicenter prospective international study. J Am Coll Cardiol. 2003, 41: 589-95.View ArticlePubMedGoogle Scholar
- Pingitore A, Picano E, Varga A, Gigli G, Cortigiani L, Previtali M, Minardi G, Colosso MQ, Lowenstein J, Mathias W, Landi P: Prognostic value of pharmacological stress echocardiography in patients with known or suspected coronary artery disease: a prospective, large scale, multicenter, head-to-head comparison between dipyridamole and dobutamine test. J Am Coll Cardiol. 1999, 6: 1769-1777. 10.1016/S0735-1097(99)00423-4.View ArticleGoogle Scholar
- Marwick TH, Case C, Sawada S, Rimmerman C, Brenneman P, Kovacs R, Short L, Lauer M: Prediction of mortality using dobutamine echocardiography. J Am Coll Cardiol. 2001, 37: 754-60.View ArticlePubMedGoogle Scholar
- Picano E, Lattanzi F, Orlandini A, Marini C, L'Abbate A: Stress echocardiography and the human factor: the importance of being expert. J Am Coll Cardiol. 1991, 17: 666-9.View ArticlePubMedGoogle Scholar
- Imran MB, Palinkas A, Pasanisi EM, De Nes M, Picano E: Optimal reading criteria in stress echocardiography. Am J Cardiol. 2002, 90: 444-5.View ArticlePubMedGoogle Scholar
- Hoffmann R, Lethen H, Marwick T, Arnese M, Fioretti P, Pingitore A, Picano E, Buck T, Erbel R, Flachskampf FA, Hanrath P: Analysis of interinstitutional observer agreement in interpretation of dobutamine stress echocardiograms. J Am Coll Cardiol. 1996, 27: 330-6.View ArticlePubMedGoogle Scholar
- Kim WY, Danias PG, Stuber M, Flamm SD, Plein S, Nagel E, Langerak SE, Weber OM, Pedersen EM, Schmidt M, Botnar RM, Manning WJ: Coronary magnetic resonance angiography for the detection of coronary stenoses. N Engl J Med. 2001, 345: 1863-9.View ArticlePubMedGoogle Scholar
- Kim RJ, Wu E, Rafael A, Chen EL, Parker MA, Simonetti O, Klocke FJ, Bonow RO, Judd RM: The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med. 2000, 343: 1445-53.View ArticlePubMedGoogle Scholar
- Nagel E, Lehmkuhl HB, Bocksch W, Klein C, Vogel U, Frantz E, Ellmer A, Dreysse S, Fleck E: Noninvasive diagnosis of ischemia-induced wall motion abnormalities with the use of high-dose dobutamine stress MRI: comparison with dobutamine stress echocardiography. Circulation. 1999, 99: 763-70.View ArticlePubMedGoogle Scholar
- Nagel E, Klein C, Paetsch I, Hettwer S, Schnackenburg B, Wegscheider K, Fleck E: Magnetic resonance perfusion measurements for the noninvasive detection of coronary artery disease. Circulation. 2003, 108: 432-7.View ArticlePubMedGoogle Scholar
- Diamond GA, Forrester JS: Analysis of probability as an aid in the clinical diagnosis of coronary artery disease. N Engl J Med. 1979, 300: 1350-1358.View ArticlePubMedGoogle Scholar
- Armstrong WF, Pellikka PA, Ryan T, Crouse L, Zoghbi WA: Stress echocardiography: recommendations for performance and interpretation of stress echocardiography. Stress Echocardiography Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography. J Am Soc Echocardiogr. 1998, 11: 97-104.View ArticlePubMedGoogle Scholar
- Dal Porto R, Faletra F, Picano E, Pirelli S, Moreo A, Varga A: Safety, feasibility, and diagnostic accuracy of accelerated high-dose dipyridamole stress echocardiography. Am J Cardiol. 2001, 87: 520-4.View ArticlePubMedGoogle Scholar
- Gibbons RJ, Balady GJ, Bricker JT, Chaitman BR, Fletcher GF, Froelicher VF, Mark DB, McCallister BD, Mooss AN, O'Reilly MG, Winters WL, Gibbons RJ, Antman EM, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Hiratzka LF, Jacobs AK, Russell RO, Smith SC: American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Committee to Update the 1997 Exercise Testing Guidelines. American College of Cardiology/American Heart Association Task Force on Practice Guidelines, Committee to Update the 1997 Exercise Testing Guidelines, ACC/AHA 2002 guideline update for exercise testing: summary article: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). J Am Coll Cardiol. 2002, 40: 1531-40.View ArticlePubMedGoogle Scholar
- Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, Pennell DJ, Rumberger JA, Ryan T, Verani MS: American Heart Association Writing Group on Myocardial Segmentation and Registration for Cardiac Imaging. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation. 2002, 105: 539-42.View ArticlePubMedGoogle Scholar
- Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise J, Solomon S, Spencer KT, St John Sutton M, Stewart W: Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005, 18: 1440-63.View ArticlePubMedGoogle Scholar
- Pennell DJ, Underwood SR, Manzara CC, Swanton RH, Walker JM, Ell PJ, Longmore DB: Magnetic resonance imaging during dobutamine stress in coronary artery disease. Am J Cardiol. 1992, 70: 34-40.View ArticlePubMedGoogle Scholar
- Baer FM, Voth E, Theissen P, Schicha H, Sechtem U: Gradient-echo magnetic resonance imaging during incremental dobutamine infusion for the localization of coronary artery stenoses. Eur Heart J. 1994, 15: 218-25.PubMedGoogle Scholar
- van Rugge FP, van der Wall EE, Spanjersberg SJ, de Roos A, Matheijssen NA, Zwinderman AH, van Dijkman PR, Reiber JH, Bruschke AV: Magnetic resonance imaging during dobutamine stress for detection and localization of coronary artery disease. Quantitative wall motion analysis using a modification of the centerline method. Circulation. 1994, 90: 127-38.View ArticlePubMedGoogle Scholar
- Hundley WG, Hamilton CA, Thomas MS, Herrington DM, Salido TB, Kitzman DW, Little WC, Link KM: Utility of fast cine magnetic resonance imaging and display for the detection of myocardial ischemia in patients not well suited for second harmonic stress echocardiography. Circulation. 1999, 100: 1697-702.View ArticlePubMedGoogle Scholar
- Pingitore A, Scattini B, De Marchi D, Acquaro G, Positano V, Deiana M, Lombardi M, Picano E: Head-to-head comparison between perfusion and wall motion during high dose dipyridamole magnetic resonance for the detection of coronary artery disease. Am J Cardiol. 2007, 101: 8-14.View ArticleGoogle Scholar
- Pennell DJ, Sechtem UP, Higgins CB, Manning WJ, Pohost GM, Rademakers FE, van Rossum AC, Shaw LJ, Yucel EK: Society for Cardiovascular Magnetic Resonance Working Group on Cardiovascular Magnetic Resonance of the European Society of Cardiology. Clinical indications for cardiovascular magnetic resonance (CMR): Consensus Panel report European Heart Journal. 2004, 25: 1940-1965.PubMedGoogle Scholar
- Picano E, Lattanzi F, Masini M, Distante A, L'Abbate A: Usefulness of the dipyridamole-exercise echocardiography test for diagnosis of coronary artery disease. Am J Cardiol. 1988, 62: 67-70.View ArticlePubMedGoogle Scholar
- Robertson WS, Feigenbaum H, Armstrong WF, Dillon JC, O'Donnell J, McHenry PW: Exercise echocardiography: a clinically practical addition in the evaluation of coronary artery disease. J Am Coll Cardiol. 1983, 2: 1085-91.View ArticlePubMedGoogle Scholar
- McNeill AJ, Fioretti PM, el-Said SM, Salustri A, Forster T, Roelandt JR: Enhanced sensitivity for detection of coronary artery disease by addition of atropine to dobutamine stress echocardiography. Am J Cardiol. 1992, 70: 41-6.View ArticlePubMedGoogle Scholar
- Sicari R, Cortigiani L, Bigi R, Landi PBSc, Raciti M, Picano E: The Prognostic value of pharmacological stress echo is affected by concomitant anti-ischemic therapy at the time of testing. Circulation. 2004, 109: 2428-2431.View ArticlePubMedGoogle Scholar
- Picano E: Informed consent and communication of risk from radiological and nuclear medicine examinations: how to escape from a communication inferno. BMJ. 2004, 329: 849-851.View ArticlePubMedPubMed CentralGoogle Scholar
- Picano E: Economic and biological costs of cardiac imaging. Cardiovasc Ultrasound. 2005, 3: 13-View ArticlePubMedPubMed CentralGoogle Scholar
- Thompson RC, Cullom SJ: Issues regarding radiation dosage of cardiac nuclear and radiography procedures. J Nucl Cardiol. 2006, 13: 19-23.View ArticlePubMedGoogle Scholar
- Einstein AJ, Moser KW, Thompson RC, Cerqueira MD, Henzlova MJ: Radiation dose to patients from cardiac diagnostic imaging. Circulation. 2007, 116: 1290-305.View ArticlePubMedGoogle Scholar
- Picano E: Stress echocardiography: a historical perspective. Am J Med. 2003, 114: 131-4.View ArticleGoogle Scholar
- Picano E, Vano E, Semelka R, Regulla D: The American College of Radiology white paper on radiation dose in medicine: deep impact on the practice of cardiovascular imaging. Cardiovasc Ultrasound. 2007, 5: 37-View ArticlePubMedPubMed CentralGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.