Dobutamine Echocardiography and Myocardial Contrast - Europe PMC

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can improve in function after revascularization. Moreover, improvements in myocardial preservation and perfusion during coronary artery bypass grafting and ...
Denton A. Cooley's 50th Anniversary in Medicine

Dobutamine Echocardiography and Myocardial Contrast Echocardiography Two New Techniques for the Assessment of Myocardial Viability

Jorge Cheirif, MD Mario Meza, MD Joseph P. Murgo, MD

This series in recognition of Dr. Cooley's 50th anniversary in medicine is continued from the December 1994 issue.

Key words: Dobutamine/diagnostic use; echocardiography/methods; heart/radionuclide imaging; technetium Tc 99m sestamibi/diagnostic use; thallium radioisotopes/ diagnostic use; tomography, emission-computed; ultrasonics/diagnostic use From: The Department of Cardiology, Section of Internal Medicine, Ochsner Medical Institutions, New Orleans, Louisiana 70121 This manuscript was written during the tenure of Clinician-Scientist Award No. 92004390 of the American Heart Association, of which Dr. Cheirif is a recipient.

Section editors: Grady L. Hallman, MD Robert D. Leachman, MD John L. Ochsner, MD Address for reprints: Jorge Cheirif, MD, Department of Cardiology, Ochsner Clinic, 1514 Jefferson Highway, New Orleans, LA 70121 Texas Hean InstituteJournal

As investigators have discovered that cardiac regions displaying resting wall motion abnormalities are not the necessary equivalent of myocardial scar (and therefore of irreversible injury) but are potentially viable regions rendered dysfunctional by stunning or hibernation, a new field of medicine has developed to identify viable myocardium that can improve in function after revascularization. Moreover, improvements in myocardial preservation and perfusion during coronary artery bypass grafting and percutaneous transluminal coronary angioplasty have enabled patients with poor resting ejection fractions to undergo safer revascularization. In this review, we describe briefly the diagnostic techniques most commonly used in identifying dysfunctional but viable myocardium. We give specific attention to the assets and limitations of these techniques and special emphasis to 2 promising new techniques: dobutamine echocardiography and myocardial contrast echocardiography. (Tex Heart Inst J 1995;22:33-9)

O ver the last few years, considerable research pertaining to the assessment of myocardial viability has been contributed to the literature. Observations that resting wall motion abnormalities frequently improve after revascularizationl'4 have stimulated the development of diagnostic techniques capable of predicting such improvements. With or without depressed ejection fraction, patients with significant left main coronary artery stenosis, with severe triple-vessel coronary artery disease, or with both, have a better survival rate when treated with aortocoronary bypass grafting than with medical therapy alone.'-8 This may indicate that patients with severe resting wall motion abnormalities have severely ischemic, yet viable, myocardium, a conjecture supported by findings that patients with coronary artery disease and asynergy frequently have significant amounts of histologically normal myocardium at autopsy.9 Furthermore, positron emission tomography (PET) shows enhanced glucose metabolism in segments that are dyskinetic or occasionally akinetic,'0° " and sometimes in "fixed" perfusion defects revealed by thallium-201 imaging.'2 Improvements in myocardial preservation and perfusion during aortocoronary bypass grafting and percutaneous transluminal coronary angioplasty (PTCA) are enabling patients with severely depressed systolic function to undergo these procedures at acceptable risk. Because revascularization of dysfunctional but viable segments may result in improved long-term vascular function and patient survival, the recognition and development of techniques that identify these segments is of utmost importance. In this review, we briefly discuss the most commonly used techniques for diagnosing and assessing myocardial viability and highlight 2 new techniques, myocardial contrast echocardiography and dobutamine echocardiography, describing specifically the ways in which they work, the criteria for their use, and their respective advantages and disadvantages.

New Techniques for Assessment of Myocardial Viability

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Methods of Assessing Myocardial Viability

TABLE 1. Criteria Used for Myocardial Viability When Using:

Several methods have been used to assess the presence or absence of myocardial viability. Generally speaking, these methods depend on the demonstration of myocardial perfusion, myocardial metabolism, or an inotropic response to a stimulus. The most established methods to date have been positron emission tomography, thallium-201 imaging, technetium Tc 99m methoxyisobutyl isonitrile (sestamibi) imaging, nitroglycerin administration, post-extrasystolic potentiation, and tissue characterization. However, recent research has indicated that 2 new methods, myocardial contrast echocardiography and dobutamine echocardiography, are extremely useful in this respect.

Criteria Are:

Positron emission tomography

* Normal '8FDG uptake * '8FDG:RBF mismatch * Moderately reduced I8FDG and RBF

Thallium-201 scintigraphy

* Normal thallium uptake * Reversible thallium defects (redistribution or post rejection) * Mild-to-moderate irreversible defects

Technetium Tc 99m methoxyisobutyl isonitrile (sestamibil) scintigraphy

* Presence of perfusion defects

Post-extrasystolic potentiation

* Improvement in contractility post PVC

Established Methods Positronz Emnission Tomography. Because of its ability to assess perfusion as well as metabolism,

Nitroglycerin administration

* Improvement in contractility after nitroglycerin administration

PET is the most reliable of the established techniques to demonstrate viability.'0"' When myocardial blood flow supply decreases, anaerobic metabolism ensues, and as a consequence the myocardium begins using glucose instead of fatty acids as a source of energy.1- The high ratio of regional glucose utilization to myocardial flow has been found by Tillisch and colleagues"' to be a reliable sign of severely ischemic but viable myocardiumn (Table I). In their study, 17 consecutive patients with resting wall miotion abnormalities were studied with PET. All patients then underwent revascularization by coronary artery bypass grafting (CABG). Seventy-three regions were found to have abnormal resting wall motion, 37 (5 1%) of which improved postoperatively (43% with mild hypokinesis, 57% with severe hypokinesis). Resting wall motion abnormalities that predicted preoperative criteria for reversible wall motion abnormalities included normal or increased "8FDG (fluorodeoxyglucose) uptake (as a tracer of metabolism). On the other hand, the criteria for irreversible abnormalities in contractility included a depressed '"NH3 uptake (as a tracer of flow) and a depressed '8FDG uptake. Postoperative improvement was seen in 35 of the 41 regions predicted to be viable by PET and in only 1 of the 13 regions predicted to be nonviable by PET. The main advantage of PET is its ability to measure, in human beings, both absolute flow in mL/min/g and myocardial metabolism. The disadvantages of PET are its high cost, the nonportability of the equipment, and need of an on-site cyclotron to produce 18FDG. Thallium-201 Imaging. Thallium-201 imaging is the most frequently used technique to assess myocardial viability. 12-1.18'-29 This stemis from 2 factors.

Tissue characterization

* Cycle-dependent amplitude modulation * Cyclic variation of integrated backscatter * Time-averaged integrated backscatter

Dobutamine echocardiography

* Improvement in regional wall motion * Thickness in response to dobutamine administration

Myocardial contrast echocardiography

* Presence of myocardial perfusion, either antegrade or retrograde

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New Techniques for Assessment of Myocardial Viability

18FDG = fluorodeoxyglucose; PVC = premature ventricular contraction; RBF = regional blood flow

First, gamma cameras used for the procedure are widely available in the United States. In addition, thallium-201 scintigraphy has been found to be a reliable technique to detect coronary artery disease and its manifestations (e.g., ischemia, myocardial infarction, and, lately, underperfused but viable myocardium). In the presence of resting wall motion abnormalities, evidence of myocardial perfusion at 4 hours after stress imaging or, alternatively, after a resting injection, suggests the presence of myocardial viability. One must be aware that a 4-hour redistribution image can lead to underestimation of myocardial viability, as a consequence of the slow nature of thallium redistribution and the low levels of thallium present in the blood hours following its administration after stress."'2" Some investigators, therefore, have suggested waiting as long as 24 hours to reassess redistribution when a fixed defect is present at 4 hours.22 However, in many cases, this V'olume 22. A'umber 1. 1995

is impractical, and in others, it can render the myocardial counts so low as to make interpretation of images difficult. To compensate for the low levels of thallium during redistribution, early or late reinjection of thallium after stress can be performed.9 Technetiium Tc 99m Methoxyisobutyl Isoniitrile (Sestamibi) Scintigraphv. Sestamibi is a relatively new radionuclide that, unlike thallium-201, does not redistribute in the myocardium. Several studies have found that its sensitivity and specificity for diagnosing coronary artery disease are comparable to those of thallium-201 scintigraphy.3"3-32 Since sestamibi's retention depends on the presence of intact sarcolemmal and mitochondrial membranes, one would expect it to be as reliable as thallium-201 in detecting viability. However, for reasons that are not well understood, this is not the case. 18.29 It is possible that investigators thus far have used threshold levels inadequate to detect viable muscle. In support of this conjecture, we have found in a preliminary study33 that sestamibi identifies viable myocardium when a low sestamibi activity threshold (20% to 30% of peak counts) is used in the asynergic regions. Future studies will need to determine what the optimal threshold values should be for this technique. Post-Extrasystolic Potentiation. The improvement in regional contractility that follows a premature ventricular beat has been used to detect viable muscle3-'35 in the presence of a regional contractile abnormality. In this regard, the criterion of viability used is similar to that applied to a dobutamine echocardiogram (i.e., if the contractile reserve improves, the region is viable). The attractiveness of this technique is its low cost, since nothing is involved but imaging while inducing the premature beat. However, one must induce the premature beat or, alternatively, wait for one to occur. Nitroglycerin Administration. Nitroglycerin has been used to detect viable but dysfunctional muscle.36-37 The mechanism of action probably arises from a reduction of preload, which decreases intracavitary pressure on the subendocardium, thereby improving the myocardial oxygen supply-anddemand ratio. Another potential effect is coronary vasodilation and, secondarily, an increase in coronary flow. Again, the main advantage of the technique is its low cost. However, nitroglycerin administration has still to prove itself in studies with high numbers of patients and in studies comparing its diagnostic accuracy with that of other techniques. Tissue Characterization. Intense research efforts are also focused on the capability of ultrasound to detect changes in the myocardium that could occur as a consequence of ischemia. The theory behind this is that ischemia induces changes in tissue composition (e.g., edema) that may alter the normal acoustic impedance of the myocardium and thereby

enable its recognition by ultrasonic means. Over the last few years, several investigators have studied the reflected ultrasonic waves from the myocardium in an effort to characterize, noninvasively, the presence of cardiac pathology."8 It has been shown that the scattering characteristics of the myocardium are affected by the presence of increased collagen39 and fibrosis-"-- during myocardial infarction-2--,5 and in certain other cardiomyopathic states.-" Among the parameters evaluated while using the tissue characterization technique, integrated backscatter power and the cyclic variation of the integrated backscatter showed significant promise in the evaluation of ischemic myocardium.`8 In a study of ischemia and reperfusion, Fitzgerald and coworkers-9 studied 20 open-chest dogs with a 5-MHz phased-array transducer. Recording of images was performed at baseline and at multiple intervals following coronary occlusion (up to 300 minutes in selected dogs). Two parameters were analyzed: the cyclic backscatter power and the total phase difference. These investigators concluded that by combining both parameters it is possible to differentiate normal, ischemic, and necrotic tissue stages. Along the same line of research, Sagar and colleagues5" used an open-chest model to study the effects of coronary occlusion and reperfusion. The 2 parameters investigated were the time-averaged integrated backscatter (TAIBS) and the cardiac cycle-dependent amplitude modulation. Following 60 minutes of occlusion, a small increase in the TAIBS was noted (p