Asrar , Sothinathan , and Roxy: Myocardial Contrast Echocardiography: Ready for the prime time.

The advancement in imaging technology coupled with development of ultrasound contrast agents (UCAs) has made it possible to detect and localize coronary artery disease at the bedside. Despite plethora of data published1, commercially available agents are still approved only for left ventricular opacification; but the true potential of these unique red blood cell tracers resides in the non-invasive assessment of myocardial perfusion during myocardial contrast echocardiography and that too with high spatial and temporal resolution than any other non-invasive bedside technique.

Several landmark publications1 in the last two decades ushered the development of myocardial perfusion imaging using UCAs and it was viewed by many to be a bright new era for MCE. However, 2007 saw regulatory authorities2 raising safety concerns and the future of MCE was put into jeopardy. Subsequent multicentre analyses on the use of UCAs3, 4, 5, and 6 included patients with a range of clinical settings and confirmed their favourable risk-benefit profile and this renewed the industry efforts to pursue for formal approval of UCAs for myocardial perfusion. What sets MCE apart from other non-invasive techniques is its ability to assess function and perfusion simultaneously in a cost effective manner.

Clinical studies have clearly demonstrated the efficacy and feasibility of myocardial contrast echocardiography for detecting perfusion abnormalities in patients with coronary artery disease7, 8 and quantifying the degree of myocardial blood flow mismatch during pharmacologic stress9, 10. Many studies have demonstrated concordance between MCE and SPECT for assessment of myocardial perfusion during rest and stress1. A meta-analysis of eight studies11 comparing sensitivity and specificity of MCE with those of SPECT/ dobutamine stress echocardiography for the detection of stable CAD showed superior sensitivity of MCE vs SPECT1. Recent multicentre studies confirmed these observations1, 12. The superior sensitivity of MCE is due to its better spatial and temporal resolution compared to SPECT. This translated into superior prediction of outcome compared to SPECT. This was demonstrated in a single centre study of approximately 300 patients where MCE was compared to SPECT-head to head13. In another head to head study, MCE was compared to cardiac magnetic resonance (CMR) for the detection of CAD14. In this study, vasodilator MCE demonstrated similar sensitivity, specificity, accuracy and reproducibility for the detection of angiographically proven CAD (defined as >70% stenosis in a major coronary artery). Achieving a favourable diagnostic performance in identifying the extent and functional significance of coronary stenosis, the overall data points out towards MCE having a sensitivity of 83% and specificity of 80% for detection of significant CAD1.

MCE also provides higher sensitivity as well as incremental prognostic value over and above wall motion (WM) in patients with stable CAD which is independent of the type of stress modality used15, 16, 17, and 18. MCE during both dobutamine stress and high-dose dipyridamole stress echocardiography provided independent and incremental prognostic information over clinical factors, resting left ventricular function and wall motion in predicting hard clinical events such as MI and death. A large (approximately 2000 patients) single centre randomised study proved that perfusion detected by MCE is superior to wall motion alone for prediction of outcomes19. Thus, when incorporating assessment of perfusion during stress echocardiography, a completely normal perfusion is very reassuring while abnormal perfusion with or without normal wall motion portends worse outcome. These results were replicated in a recent study20 when MCE was incorporated into the routine clinical stress echocardiography service. It provided incremental diagnostic information not only for the detection of CAD but also for the assessment of the extent of ischemia compared to wall motion abnormality alone. This resulted in incremental prognostic outcome provided by MCE which assesses function and perfusion simultaneously21. The wealth of data resulted in recommendation in the recent stable angina guidelines by the European Society of Cardiology for the use of MCE in daily clinical practice to enhance the diagnostic value of stress echocardiography22.

The pathophysiological rationale of MCE is simple, based on the ischemic cascade where perfusion abnormalities appear earlier than wall motion abnormalities. This accounts for the better sensitivity of perfusion compared with wall motion for the detection of CAD. Perfusion defects may also occur in absence of significant CAD (e.g. myocardial hypertrophy) and suggest microvascular dysfunction, with higher risk of cardiovascular events. Overall, the ability to assess function and perfusion simultaneously during rest and stress asserts the potential of MCE to be a useful bedside diagnostic tool. Clinical studies have demonstrated the potential of this technique in assessment of acute chest pain in the emergency department, detection of viability, and various other clinical scenarios with optimum accuracy1.

MCE is a technique that has come of age and the time is overdue for it to be incorporated into routine clinical use as recommended by the European guidelines. However, it needs to be emphasized that like all imaging techniques, training and expertise are required to achieve such results1. There has to be a concerted effort by all stake-holders to make this happen and bring the technology right at the door-steps of patient care. Moreover, without commitment of trainers and trainees to teach and be taught, it is unlikely that significant progress can be made and the technique may remain unrealised forever. Undoubtedly, MCE holds great clinical promise rather than remaining a technique with potential un-fulfilled.



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