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Historical and Landmark Papers

Contrast Echo Box: Key Reference Library

Find out more about Contrast Echocardiography by exploring the Contrast Echo Box

Impact of Contrast Echocardiography on Evaluation of Ventricular Function and Clinical Management in a Large Prospective Cohort

Kurt M, Shaikh KA, Peterson L, Kurrelmeyer KM, Shah G, Nagueh SF, Fromm R, Quinones MA, Zoghbi WA.
632 patients with technically challenging echo windows, who thus received contrast agent(s), were prospectively enrolled. After contrast, the percent of uninterpretable studies decreased from 11.7% to 0.3% and technically difficult studies decreased from 86.7% to 9.8% (p< 0.0001). Before contrast, 11.6± 3.3 of 17 LV segments were seen, which improved after contrast to 16.8±1.1 (p< 0.0001). A significant impact on management was observed: additional diagnostic procedures were avoided in 32.8% of patients and drug management was altered in 10.4%, total impact (procedures avoided, change in drugs, or both) in 35.6% of patients. A cost–benefit analysis showed a significant savings using contrast ($122/patient).
Reference: J Am Coll Cardiol. 2009; 53(9); 802-10

Myocardial contrast echocardiography for distinguishing ischemic from nonischemic first-onset acute heart failure: insights into the mechanism of acute heart failure

Senior R, Janardhanan R, Jeetley P, Burden L.
This study was the first to prove the value of MCE in identifying aetiology (ischaemic vs non-ischaemic) in patients presenting for the first time with heart failure. 52 patients with acute heart failure but no prior cardiac history underwent rest and stress MCE prior to cardiac catheterisation. Sensitivity, specificity, positive and negative predictive values for MCE to detect a >50% coronary stenosis were 82%, 97%, 95% and 88% respectively.
Reference: Circulation 2005;112(11):1587-93

Comparative accuracy of real-time myocardial contrast perfusion imaging and wall motion analysis during dobutamine stress echocardiography for the diagnosis of coronary artery disease

Elhendy A, O'Leary EL, Xie F, McGrain AC, Anderson JR, Porter TR.
This was the first study to show that perfusion assessment has incremental benefit over wall motion analysis in detecting CAD. 170 patients underwent MCE during dobutamine stress echocardiography prior to coronary angiography. MCE was more sensitive than wall motion analysis for detecting CAD (>50% stenosis on angiography) at peak and intermediate stress. Overall accuracy was higher for MCE than for WMA (81% vs. 71%; p = 0.01).
Reference: J Am Coll Cardiol. 2004; 44 (11); 2185-91

Intravenous myocardial contrast echocardiography predicts recovery of dyssynergic myocardium early after acute myocardial infarction

Swinburn JM, Lahiri A & Senior R.
The first paper to show that delayed imaging (1:10) is the technique of choice for detecting myocardial viability. 96 patients with recent acute MI underwent echocardiography at baseline and 6 months later or 3 months after revascularization to determine regional function. MCE was performed at baseline using triggering intervals of 1:1 (early) and 1:10 (delayed) cardiac cycles. Delayed imaging had superior positive and negative predictive value for recovery of systolic function. The authors concluded that delayed triggered MCE can independently detect myocardial viability early after AMI and that delayed triggered imaging is superior to early triggered imaging.
Reference: J Am Coll Cardiol 2001; 38(1):19-25.

Real-time assessment of myocardial perfusion and wall motion during bicycle and treadmill exercise echocardiography: comparison with single photon emission computed tomography

Shimoni S, Zoghbi WA, Xie F, Kricsfeld D, Iskander S, Gobar L, Mikati IA, Abukhalil J, Verani MS, O’Leary, Porter TR.
One of the first studies to demonstrate the feasibility and accuracy of low-power real-time MCE using exercise stress (n=50 bicycle, n=50 treadmill) as opposed to pharmacological stress. MCE correlated well with SPECT imaging and sensitivity and specificity for detecting CAD (defined on angiography) were 75% and 81% respectively. The best diagnostic accuracy (86%) was seen when perfusion (MCE) and wall motion findings were combined.
Reference: J Am Coll Cardiol 2001; 37 (3); 741-47

Role of capillaries in determining CBF reserve: new insights using myocardial contrast echocardiography

Jayaweera AR, Wei K, Coggins M, Ping Bin J, Goodman C, Kaul S.
Landmark study which proved, for the first time, that capillaries play a crucial role in regulation of coronary blood flow (CBF). A canine model of the coronary circulation with three compartments was created (arterial, capillary, venous). In a normal state, capillaries contributed just 25% of the total myocardial vascular resistance at rest but this rose to 75% during maximal hyperaemia, despite total myocardial vascular resistance falling. In the presence of a non-critical stenosis, total myocardial vascular resistance increased during hyperaemia predominantly due to increased capillary resistance. Thus, contrary to widely held beliefs at that time, capillaries were shown to participate in CBF regulation.
Reference: Am J Physiol Heart Circ Physiol 1999; 277; H2363-H237

Quantification of myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a constant venous infusion

Wei K, Jayaweera AR, Firoozan S, Linka A, Skyba DM, Kaul S.
Landmark study that provided proof for the physiological basis of quantification of MCE by studying bubble and ultrasound interaction. Myocardial blood flow (MBF) studied in ex-vivo and in-vivo experimental models in 21 dogs. Demonstrated that the peak video intensity (A) reflected myocardial blood volume and that the slope of the curve obtained by plotting video intensity against pulsing interval was equal to the microbubble velocity (β). The product (A x β) gives myocardial blood flow.
Reference: Circulation 1998;97(5):473-83

An association between collateral blood flow and myocardial viability in patients with recent myocardial infarction

Sabia PJ, Powers ER, Ragosta M, Sarembock IJ, Burwell LR, Kaul S.
Regional LV systolic function was assessed before and one month after attempted angioplasty in 43 patients with recent (<5weeks) myocardial infarction (MI) resulting in an occluded infarct-related artery (IRA). It was shown that collateral-derived residual flow is common in such patients and that it can maintain viability for several weeks. Moreover, the degree of improvement of regional function after revascularisation was related to the percentage of the occluded bed perfused by collateral flow. The authors concluded that viability appears to be directly associated with the presence of collateral blood flow within the infarct bed.
Reference: N Engl J Med 1992; 327: 1825-1831

Safety and efficacy of a new transpulmonary ultrasound contrast agent: initial multicenter clinical results

Feinstein SB, Cheirif J, Ten Cate FJ, Silverman PR, Heidenreich PA, Dick C, Desir RM, Armstrong WF, Quinones MA, Shah PM
The first study in man using Albunex – sonicated albumin – contrast agent. Safety was proven, but only 63% of injections were judged to cause adequate LV opacification.
J Am Coll Cardiol 1990; 16(2):316-24

Two-dimensional contrast echocardiography: In vitro development and quantitative analysis of echo contrast agents

Feinstein SB, Ten Cate FJ, Zwehl W, Ong K, Maurer G, Tei C, et al.
Classic study that showed that ‘sonication’ of dextrose / sorbitol solutions (exposure to ultrasonic energy) produced small, uniform and stable microbubbles capable of opacifying the LV and could be used as ultrasound contrast agents.
Reference: J Am Coll Cardiol 1984;3(1):14-20

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