LETTERS TO THE EDITOR doi:10.1093/jer279 Online publish-ahead-of-print 22 December 2011 Bolus injection or continuous infusion for the assessment of myocardial blood flow during perfusion stress echocardiography? We read the recent article by Wejner-Mik et al. 1 in the Journal with great interest and we congratulate them on their study which re-emphasizes both the clinical value of myo- cardial contrast echocardiography (MCE) and specifically the prognostic value of dipyrid- amole MCE. Both real-time and triggered imaging techniques were used, highlighting the robust nature of each method. We wish to highlight certain methodological aspects which may be of use in planning future studies. First, the contrast agent (Optison) was administered by repeated bolus injections rather than a continuous intravenous infusion. The pioneering scientific experiments that established the ability of MCE to assess myo- cardial blood flow (MBF) used a continuous infusion. 2 The myocardial signal assessed visu- ally as contrast intensity reflects the concen- tration of microbubbles within the myocardium. When the entire myocardium is fully saturated with microbubbles, the signal intensity denotes the capillary blood volume. 3 Any alteration of signal must, there- fore, occur predominantly from a change in capillary blood volume. Consequently, one of the basic physiological principles of MCE is that the myocardium should be fully satu- rated with microbubbles prior to destruction- replenishment imaging. This steady-state can be achieved with a bolus injection if the microbubbles persist for long-time periods (e.g. as with the contrast agent Imagify w , used in the recent multicentre RAMP trials). 4 Continuous infusion of contrast has several other advantages. 5 First, titrating the rate of infusion allows one to individualize the dose needed for each patient, secondly there is more time to acquire images with an infusion, whereas with a bolus injection the degree of opacification deteriorates rapidly with time, thirdly there are reduced contrast artefacts with infusion use (e.g. shadowing, blooming, or swirling) and, fourthly, use of an infusion allows quantification of MBF. Additionally, cal- culation of MBF at rest and stress yields the coronary flow reserve, which has both diag- nostic and prognostic benefit in a variety of conditions. The EAE guidelines on contrast echocardiography 6 recommend continuous infusion for the assessment of myocardial perfusion. Secondly, as the authors themselves ac- knowledge, the population studied were a high-risk cohort—all had been referred on clinical grounds for cardiac catheterization and, indeed, 75% were found to have signifi- cant coronary artery disease. We therefore propose that further studies in a low- intermediate risk cohort will also be of clinical value, as it is frequently such patients in whom functional imaging tests are requested. In conclusion, we again commend the authors on their work and for achieving lengthy follow-up in a large cohort to inform us of the prognostic significance of di- pyridamole MCE in a high-risk patient popula- tion. However, we have certain methodological suggestions as described above and, in particular, propose that the optimal method for assessing myocardial per- fusion during MCE is with a continuous intra- venous infusion of contrast. References 1. Wejner-Mik P, Lipiec P, Kasprzak JD. Long-term prognostic value of dipyridamole stress myocardial contrast echocardiography. Eur J Echocardiogr 2011; 12:762–6. 2. Wei K, Jayaweera AR, Firoozan S, Linka A, Skyba DM, Kaul S. Quantification of myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a constant venous in- fusion. Circulation 1998;97:473–83. 3. Linka AZ, Sklenar J, Wei K, Jayaweera AR, Skyba DM, Kaul S. Assessment of transmural distribution of myocardial perfusion with contrast echocardiog- raphy. Circulation 1998;98:1912–20. 4. Senior R, Monaghan M, Main ML, Zamorano JL, Tiemann K, Agati L et al. Detection of coronary artery disease with perfusion stress echocardiog- raphy using a novel ultrasound imaging agent: two Phase 3 international trials in comparison with radio- nuclide perfusion imaging. Eur J Echocardiogr 2009;10: 26–35. 5. Wei K, Jayaweera AR, Firoozan S, Linka A, Skyba DM, Kaul S. Basis for detection of stenosis using venous administration of microbubbles during myocardial contrast echocardiography: bolus or con- tinuous infusion? J Am Coll Cardiol 1998;32:252 – 60. 6. Senior R, Becher H, Monaghan M, Agati L, Zamorano J, Vanoverschelde JL et al. Contrast echo- cardiography: evidence-based recommendations by European Association of Echocardiography. Eur J Echocardiogr 2009;10:194 – 212. Benoy Nalin Shah* Roxy Senior Department of Echocardiography, Royal Brompton Hospital and Imperial College, Sydney Street, London SW3 6NP, United Kingdom *Corresponding author. Tel: +44 207 349 7740, fax: +44 207 351 8604, Email: benoy@doctors. org.uk doi:10.1093/ehjci/jer280 Online publish-ahead-of-print 22 December 2011 Bolus injection for the assessment of perfusion during stress echocardiography has several limitations, but also certain advantages We would like to thank Dr Shah and Professor Senior 1 for their interest in our recent article regarding the prognostic value of stress myocardial contrast echo- cardiography (MCE) 2 and for their insightful comments concerning methodology of our study. Indeed, contrast administration by bolus injections has several limitations, such as un- suitability for advanced quantitative analysis, decreased diagnostic time window and more risk of acoustic shadowing affecting the far field image quality. 3 – 5 It is true that the calculation of myocardial blood flow and replenishment curve-derived quantitative indices requires a stable microbubbles con- centration. All the benefits from infusion notwithstanding, we believe that slow manual administration of individually adjusted boluses of contrast can provide satisfactory images for qualitative analysis. In our previ- ous study based on bolus injections of con- trast, perfusion assessment by real-time MCE was precluded by suboptimal image quality only in 5% of segments at rest and in 5.2% during stress. 6 According to our ex- perience, this is partly due to the immediate visual feedback between myocardial signal in- tensity and the rate of injection. Thus, we hypothesized in our study that visually assessed differences in myocardial contrast intensity may provide valuable prognostic Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2011. For permissions please email: journals.permissions@oup.com Downloaded from https://academic.oup.com/ehjcimaging/article/13/1/118/2397324 by guest on 08 January 2022