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How good is echocardiography at assessing myocardial viability?
How Good Assessing
Is Echocardiography Myocardial Wability? Paul A. Grayburn,
at
MD
n patients with coronary artery disease, resting wall Imyocardial motion abnormalities may be a permanent result of necrosis or a reversible consequence of tran-
MCE has been used extensively in animal and human research over the past 10 years and provides the ability to assess regional perfusion and contractile function sient ischemia, myocardial stunning, or hibernating myo- simultaneously. Briefly, an echocardiographic contrast cardium.’ Detection of perfusion, metabolic activity, or agent, either sonicated angiographic contrast or comcontractile reserve within a dysfunctional myocardial mercially prepared albumin-coated microbubbles, is desegment indicates that the segment is “viable” and capa- livered by intracoronary injection during cardiac cathble of functional recovery after coronary revascularizaeterization. The microbubbles are approximately the size tion. There are 2 echocardiographic methods to assess of red blood cells and thus are small enough to pass myocardial viability: dobutamine stress echocardiogthrough the coronary microcirculation where they are raphy (DSE), which detects contractile reserve, and myo- easily visualized echocardiographicahy as an echo-dense cardial contrast echocardiography (MCE), which detects blush in the myocardium. The safety of myocardial conmyocardial perfusion. I will review the current and trast agents has been well documented, and the hemopotential uses of DSE and MCE in assessing myocardial dynamic effects of sonicated angiographic contrast are viability, with an emphasis on their ability to predict left identical to those seen with nonsonicated contrast in ventricular (LV) functional recovery after revascularizahumans and animal models. tion. In patients with acute myocardial infarction, MCE Contractile reserve is the ability to elicit contractile has shown collateral flow to the infarct zone despite totalimprovement of a regional wall motion abnormality in ly occluded infarct arteries. 14,15Patients with collateral response to an inotropic stimulus. In patients with de- perfusion of the infarct zone by MCE have better regionpressed LV function, contractile reserve has important al LV function than those without collaterals.15 Moreprognostic implications in patients being considered for over, collateral perfusion of >50% of the infarct zone bypass surgery. 2,3 Prior studies used ventriculography to predicts improvement in wall motion 1 month after sucdetect contractile reserve during infusion of epinephrine cessful angioplasty of an occluded infarct artery.15 or nitroglycerin, or after premature ventricular contrac- Recent studies suggest that perfusion by MCE can pretions.2,3 DSE uses a graded infusion of dobutamine to dict recovery of LV function after myocardial infarcelicit improvement in regional systolic wall thickening tion16,17 and after revascularization in patients with in areas of resting wall motion abnormality. Contractile chronic ischemic heart disease.9 Although such studies are promising, MCE is limited by the requirement for reserve by DSE has generally been defined as improved systolic wall thickening in 22 adjacent abnormal seg- intracoronary injection of the contrast agent. Newer conmentsb9. 1 study also required an improvement of 220% trast agents that are capable of, crossing the pulmonary (i.e., the’95% confidence level) in wall motion score circulation via peripheral venous injection are being index.4 developed. One such agent has recently been shown to The ability of DSE to predict LV functional recov- accurately define myocardial area at risk and infarct size ery after bypass surgery or angioplasty in patients with from a peripheral venous injection in the canine model chronic ischemic heart disease has been established in 6 of acute myocardial ischemia.18 If safe and effective instudies consisting of 157 patients.4-9 In these studies, the travenous contrast agents become available for human positive predictive value of DSE in predicting LV func- use, MCE could be performed at the bedside in the corotional recovery after revascularization ranged from 72% nary care unit or emergency department. This could to 91%. The negative value of DSE in predicting lack of allow noninvasive identification of the size and location functional recovery ranged from 77% to 94%. A total of of a perfusion defect in patients with suspected myocar4 studies consisting of 146 patients have shown that con- dial infarction. Repeat MCE after thrombolytic therapy tractile reserve during DSE predicts improved regional could potentially determine the success of reperfusion LV function after acute myocardial infarction.“13 In and/or the need for salvage angioplasty. Two studies have directly compared perfusion and these studies, the positive predictive value ranged from 60% to 90% and the negative predictive value from 88% contractile reserve in predicting recovery of LV function to 100%. in patients with chronic ischemic heart disease. Amese et al7 compared poststress thallium reinjection and DSE in 38 patients with chronic ischemic heart disease and From the Department of Internal Medicine, University of Texas SouthLV ejection fraction ~0.40. In these patients, 170 akiwestern and Veterans Affairs Medical Centers, Dallas, Texas. Manu netic or severely hypokinetic segments were successfulscript received and accepted August 22, 1995. ly revascularized. Perfusion was present by thallium Address for reprints: Paul A. Grayburn, MD, Division of Cardi. scintigraphy in 103 segments (61%), whereas only 33 ology, University of Texas Southwestern Medical Center. 5323 Harry Hines Boulevard, Dallas, Texas 75235.9047 segments (19%) had contractile reserve by DSE (p EDITORIALS
1183
THE AMERICAN
JOURNAL
OF CARDIOLOGY@
VOL. 76
related to the timing of early reperfusion. Because of its great potential to identify myocardial area at risk, collateral flow, and reperfusion in the early postinfarction period, MCE may prove to be superior in assessing myocardial viability in acute myocardial infarction, particularly if safe and effective intravenous contrast agents become available.
I. Brannwald E, Rutherford JD. Reversible ischemic left ventricular dysfunction: evidence for the “hibernating myocardium.” JAm Coil Car&l 19X&8:1467-1470. 2. Nesto RW, Cohn LH, Collins JJ, Wynne J, Holman L, Cohn PF. Inotropic contractile reserve: a useful predictor of increased 5-year survival and improved postoperative left ventricular function in patients with coronary artery disease and reduced ejection fraction. Am J Cardiol 1982;50:39-44. 3. Popio KA, Gorlin R, Bechtel D, Levine JA. Postextrasystolic potent&ion as a predictor of potential myocardial viability: preoperative analyses compared with studies after coronary bypass surgery. Am J Cardiol 1977;39:944-951. 4. Cigarroa CG, deFilippi CR, Brickner ME, Alvarez LG, Wait MA, Graybum PA. Dobntamine stress echocardiography identifies hibernating myocardium and predicts recovery of left ventricular function after coronary revascularization. Circulation 1993;88:430-436. 5. La Canna G, Alfieri 0, Giubbini R, Gargano M, Ferrari R, Visioli 0. Echocardiography during infusion of dobutamine for identification of reversible dysfunction in patients with chronic coronary artery disease. J Am Coil Cardiol 1994;23: 617-626. 6. Afridi I, Kleiman NS, Raizner AE, Zoghbi WA. Dobutamine echocardiography
in myocardial hibernation: optimal dose and accuracy iti predicting recovery of ventricular function after coronary angioplasty. Circulation 199.5;91:663670. 7. Amese M, Come1 JH, Salustri A, Maat APWM, Elhendy A, Reijs AEM, ten Gate FJ, Keane D, Balk AHMM, Roelandt JRTC, Fiorefti PM. Prediction of improvement of regional left ventricular function after surgical revascularization: a comparison of low-dose dobutamine echocardiography with Z”‘TI single-photon emission computed tomography. Circulation 1995;91:2748-2752. 8. Perrone-Filardi P; Pace L, Prastaro M, Piscione F, Betocchi S, Squame F, Vezzuto P, Soricelli A, Indolfi C, Salvatore M, Chiarello M. Dobutamine echocardiography predicts improvement of hypoperfosed dysfunctional myocardium after revascularization in patients with coronary attery disease. Circulation 1995;91: 2556-2565. 9. deFilippi CR, Willett DL, Irani WN, Eichhom EJ, Velasco CE, Graybum PA.
Comparison of myocardial contrast echocardiography and dobutamine stress echocardiography in predicting recovery of regional left ventricular function after coronary revascularization. Circularion 1995; in press. IO. Pierard LA, de Landsheere CM, Berthe C, Rigo P, Kulbertas HE. Identification of viable myocaxlium by echocardiography during dobutamine infusion in patients with myocardial infarction after thrombolytic therapy: comparison with positron emission tomography. J Am Coil Cardiol 1990,15:1021-iO31. I I. Barilla F, Gheorghiade KP, Alam M, Khaja F, Goldstein S. Low dose dobutamine in patients with acute myocardial infarction identifies viable but not contractile myocardium and predicts the magnitude of improvement in wall motion abnormalities in response to coronary revascularization. Am Heart J 1991;122: 1522-1531. 12. Smart SC, Sawada S, Ryan T, Segar D, Atherton L, Berkovitz K, Boordillon PDV, Feigenbaum H. Low-dose dobutamine echocardiography detects reversible dysfunction after thrombdytic therapy of acute myocardial infarction. Circulation 1993;88:405-415. 13. Silvestri A, Elhendy A, Gatyfallydis P, Ciavatti M, Come1 JH, ten Gate FJ, Boersma E, Gernelli A, Roelandt JRTC, Fioretti PM. Prediction of improvement of ventricular function after first acute myocardial infarction using low-dose dobutamine stress echocardiogr8phy. Am J Cardiol 1994;74:853-856. 14. Sabia PJ, Powers ER, Jayaweera AR, Ragosta M, Kaul S. Functional significance of collateral blood flow in patients with recent acute myocxdial infarction. Circulafion 1992;85:208&2089. 15. Sabia PJ, Powers ER, Ragosta M, Sarembock IJ, Burwell LR, Kaul S. An association between collateral blood flow and myocardial viability in patients with recent myocardial infarction. N Engl .I Med 1992;327:1825-1831. 16. Ragosta M, Camarano G, Kaul S, Powers ER, Sarembock IJ, Gimple LW. Microvascular integrity indicates myocellular viability in patients with recent myocardial infarction: new insights using myocardial contrast echocardiography. Circulation 1994;89:2562-2569. 17. Cqarano G, Ragosta M, Gimple LW, Powers ER, Kaul S. Identification of viable myocardium with contrast echocardiography in patients with poor left ventricular systolic function caused by recent or remote myocardial infarction. Am J Cardiol 1995;75:215-219. 18. Grayborn PA, Erikson JM, Escobar J, Womack L, Velasco CE. Peripheral intravenous myocardial contrast echocardiography using a 2% dodecafluoropentane emulsion: identification of myocardial risk area and infarct size in the canine model of ischemia. 3 Am Co11 Cardiol 1995; in press. 19. Bodenheimer MM, Banka VS, Hermann GA, Trout RG, Pasdar H, Helfant R. Reversible asynergy: histopathologic and electrocardiographic correlations in patients with coronary artery disease. Circulation 1976;53:792-196. DECEMBER
1, 1995
Is Echocardiography Myocardial Wability? Paul A. Grayburn,
at
MD
n patients with coronary artery disease, resting wall Imyocardial motion abnormalities may be a permanent result of necrosis or a reversible consequence of tran-
MCE has been used extensively in animal and human research over the past 10 years and provides the ability to assess regional perfusion and contractile function sient ischemia, myocardial stunning, or hibernating myo- simultaneously. Briefly, an echocardiographic contrast cardium.’ Detection of perfusion, metabolic activity, or agent, either sonicated angiographic contrast or comcontractile reserve within a dysfunctional myocardial mercially prepared albumin-coated microbubbles, is desegment indicates that the segment is “viable” and capa- livered by intracoronary injection during cardiac cathble of functional recovery after coronary revascularizaeterization. The microbubbles are approximately the size tion. There are 2 echocardiographic methods to assess of red blood cells and thus are small enough to pass myocardial viability: dobutamine stress echocardiogthrough the coronary microcirculation where they are raphy (DSE), which detects contractile reserve, and myo- easily visualized echocardiographicahy as an echo-dense cardial contrast echocardiography (MCE), which detects blush in the myocardium. The safety of myocardial conmyocardial perfusion. I will review the current and trast agents has been well documented, and the hemopotential uses of DSE and MCE in assessing myocardial dynamic effects of sonicated angiographic contrast are viability, with an emphasis on their ability to predict left identical to those seen with nonsonicated contrast in ventricular (LV) functional recovery after revascularizahumans and animal models. tion. In patients with acute myocardial infarction, MCE Contractile reserve is the ability to elicit contractile has shown collateral flow to the infarct zone despite totalimprovement of a regional wall motion abnormality in ly occluded infarct arteries. 14,15Patients with collateral response to an inotropic stimulus. In patients with de- perfusion of the infarct zone by MCE have better regionpressed LV function, contractile reserve has important al LV function than those without collaterals.15 Moreprognostic implications in patients being considered for over, collateral perfusion of >50% of the infarct zone bypass surgery. 2,3 Prior studies used ventriculography to predicts improvement in wall motion 1 month after sucdetect contractile reserve during infusion of epinephrine cessful angioplasty of an occluded infarct artery.15 or nitroglycerin, or after premature ventricular contrac- Recent studies suggest that perfusion by MCE can pretions.2,3 DSE uses a graded infusion of dobutamine to dict recovery of LV function after myocardial infarcelicit improvement in regional systolic wall thickening tion16,17 and after revascularization in patients with in areas of resting wall motion abnormality. Contractile chronic ischemic heart disease.9 Although such studies are promising, MCE is limited by the requirement for reserve by DSE has generally been defined as improved systolic wall thickening in 22 adjacent abnormal seg- intracoronary injection of the contrast agent. Newer conmentsb9. 1 study also required an improvement of 220% trast agents that are capable of, crossing the pulmonary (i.e., the’95% confidence level) in wall motion score circulation via peripheral venous injection are being index.4 developed. One such agent has recently been shown to The ability of DSE to predict LV functional recov- accurately define myocardial area at risk and infarct size ery after bypass surgery or angioplasty in patients with from a peripheral venous injection in the canine model chronic ischemic heart disease has been established in 6 of acute myocardial ischemia.18 If safe and effective instudies consisting of 157 patients.4-9 In these studies, the travenous contrast agents become available for human positive predictive value of DSE in predicting LV func- use, MCE could be performed at the bedside in the corotional recovery after revascularization ranged from 72% nary care unit or emergency department. This could to 91%. The negative value of DSE in predicting lack of allow noninvasive identification of the size and location functional recovery ranged from 77% to 94%. A total of of a perfusion defect in patients with suspected myocar4 studies consisting of 146 patients have shown that con- dial infarction. Repeat MCE after thrombolytic therapy tractile reserve during DSE predicts improved regional could potentially determine the success of reperfusion LV function after acute myocardial infarction.“13 In and/or the need for salvage angioplasty. Two studies have directly compared perfusion and these studies, the positive predictive value ranged from 60% to 90% and the negative predictive value from 88% contractile reserve in predicting recovery of LV function to 100%. in patients with chronic ischemic heart disease. Amese et al7 compared poststress thallium reinjection and DSE in 38 patients with chronic ischemic heart disease and From the Department of Internal Medicine, University of Texas SouthLV ejection fraction ~0.40. In these patients, 170 akiwestern and Veterans Affairs Medical Centers, Dallas, Texas. Manu netic or severely hypokinetic segments were successfulscript received and accepted August 22, 1995. ly revascularized. Perfusion was present by thallium Address for reprints: Paul A. Grayburn, MD, Division of Cardi. scintigraphy in 103 segments (61%), whereas only 33 ology, University of Texas Southwestern Medical Center. 5323 Harry Hines Boulevard, Dallas, Texas 75235.9047 segments (19%) had contractile reserve by DSE (p EDITORIALS
1183
THE AMERICAN
JOURNAL
OF CARDIOLOGY@
VOL. 76
related to the timing of early reperfusion. Because of its great potential to identify myocardial area at risk, collateral flow, and reperfusion in the early postinfarction period, MCE may prove to be superior in assessing myocardial viability in acute myocardial infarction, particularly if safe and effective intravenous contrast agents become available.
I. Brannwald E, Rutherford JD. Reversible ischemic left ventricular dysfunction: evidence for the “hibernating myocardium.” JAm Coil Car&l 19X&8:1467-1470. 2. Nesto RW, Cohn LH, Collins JJ, Wynne J, Holman L, Cohn PF. Inotropic contractile reserve: a useful predictor of increased 5-year survival and improved postoperative left ventricular function in patients with coronary artery disease and reduced ejection fraction. Am J Cardiol 1982;50:39-44. 3. Popio KA, Gorlin R, Bechtel D, Levine JA. Postextrasystolic potent&ion as a predictor of potential myocardial viability: preoperative analyses compared with studies after coronary bypass surgery. Am J Cardiol 1977;39:944-951. 4. Cigarroa CG, deFilippi CR, Brickner ME, Alvarez LG, Wait MA, Graybum PA. Dobntamine stress echocardiography identifies hibernating myocardium and predicts recovery of left ventricular function after coronary revascularization. Circulation 1993;88:430-436. 5. La Canna G, Alfieri 0, Giubbini R, Gargano M, Ferrari R, Visioli 0. Echocardiography during infusion of dobutamine for identification of reversible dysfunction in patients with chronic coronary artery disease. J Am Coil Cardiol 1994;23: 617-626. 6. Afridi I, Kleiman NS, Raizner AE, Zoghbi WA. Dobutamine echocardiography
in myocardial hibernation: optimal dose and accuracy iti predicting recovery of ventricular function after coronary angioplasty. Circulation 199.5;91:663670. 7. Amese M, Come1 JH, Salustri A, Maat APWM, Elhendy A, Reijs AEM, ten Gate FJ, Keane D, Balk AHMM, Roelandt JRTC, Fiorefti PM. Prediction of improvement of regional left ventricular function after surgical revascularization: a comparison of low-dose dobutamine echocardiography with Z”‘TI single-photon emission computed tomography. Circulation 1995;91:2748-2752. 8. Perrone-Filardi P; Pace L, Prastaro M, Piscione F, Betocchi S, Squame F, Vezzuto P, Soricelli A, Indolfi C, Salvatore M, Chiarello M. Dobutamine echocardiography predicts improvement of hypoperfosed dysfunctional myocardium after revascularization in patients with coronary attery disease. Circulation 1995;91: 2556-2565. 9. deFilippi CR, Willett DL, Irani WN, Eichhom EJ, Velasco CE, Graybum PA.
Comparison of myocardial contrast echocardiography and dobutamine stress echocardiography in predicting recovery of regional left ventricular function after coronary revascularization. Circularion 1995; in press. IO. Pierard LA, de Landsheere CM, Berthe C, Rigo P, Kulbertas HE. Identification of viable myocaxlium by echocardiography during dobutamine infusion in patients with myocardial infarction after thrombolytic therapy: comparison with positron emission tomography. J Am Coil Cardiol 1990,15:1021-iO31. I I. Barilla F, Gheorghiade KP, Alam M, Khaja F, Goldstein S. Low dose dobutamine in patients with acute myocardial infarction identifies viable but not contractile myocardium and predicts the magnitude of improvement in wall motion abnormalities in response to coronary revascularization. Am Heart J 1991;122: 1522-1531. 12. Smart SC, Sawada S, Ryan T, Segar D, Atherton L, Berkovitz K, Boordillon PDV, Feigenbaum H. Low-dose dobutamine echocardiography detects reversible dysfunction after thrombdytic therapy of acute myocardial infarction. Circulation 1993;88:405-415. 13. Silvestri A, Elhendy A, Gatyfallydis P, Ciavatti M, Come1 JH, ten Gate FJ, Boersma E, Gernelli A, Roelandt JRTC, Fioretti PM. Prediction of improvement of ventricular function after first acute myocardial infarction using low-dose dobutamine stress echocardiogr8phy. Am J Cardiol 1994;74:853-856. 14. Sabia PJ, Powers ER, Jayaweera AR, Ragosta M, Kaul S. Functional significance of collateral blood flow in patients with recent acute myocxdial infarction. Circulafion 1992;85:208&2089. 15. Sabia PJ, Powers ER, Ragosta M, Sarembock IJ, Burwell LR, Kaul S. An association between collateral blood flow and myocardial viability in patients with recent myocardial infarction. N Engl .I Med 1992;327:1825-1831. 16. Ragosta M, Camarano G, Kaul S, Powers ER, Sarembock IJ, Gimple LW. Microvascular integrity indicates myocellular viability in patients with recent myocardial infarction: new insights using myocardial contrast echocardiography. Circulation 1994;89:2562-2569. 17. Cqarano G, Ragosta M, Gimple LW, Powers ER, Kaul S. Identification of viable myocardium with contrast echocardiography in patients with poor left ventricular systolic function caused by recent or remote myocardial infarction. Am J Cardiol 1995;75:215-219. 18. Grayborn PA, Erikson JM, Escobar J, Womack L, Velasco CE. Peripheral intravenous myocardial contrast echocardiography using a 2% dodecafluoropentane emulsion: identification of myocardial risk area and infarct size in the canine model of ischemia. 3 Am Co11 Cardiol 1995; in press. 19. Bodenheimer MM, Banka VS, Hermann GA, Trout RG, Pasdar H, Helfant R. Reversible asynergy: histopathologic and electrocardiographic correlations in patients with coronary artery disease. Circulation 1976;53:792-196. DECEMBER
1, 1995