Identification of hibernating myocardium with myocardial contrast echocardiography

International Journal of Cardiology 128 (2008) 117 – 120 www.elsevier.com/locate/ijcard

Letter to the Editor

Identification of hibernating myocardium with myocardial contrast echocardiography ☆ Comparison with late gadolinium-enhanced magnetic resonance Petr Tousek a,⁎, Martin Penicka a , Jaroslav Tintera b , Hana Linkova a , Pavel Gregor a a

Cardiocenter, Department of Cardiology, 3rd Faculty of Medicine, Charles University and University Hospital Kralovske Vinohrady Prague, Ruska 87, 100 00 Prague, Czech Republic b Institute of Clinical and Experimental Medicine, Prague, Czech Republic Received 12 March 2007; accepted 26 May 2007 Available online 29 August 2007

Abstract Very little is known about the accuracy of intravenous myocardial contrast echocadiography (MCE) in the detection of myocardial hibernation. There are also currently no data on the comparison of MCE to late gadolinium-enhanced magnetic resonance (LGE-MR) in this clinical setting. The aim of this pilot study was to predict recovery of regional function in patients with ischemic LV dysfunction undergoing bypass surgery and to compare the accuracy of MCE with LGE-MR in this clinical setting. The sensitivity of preserved myocardial perfusion during MCE for segmental function recovery (hibernating myocardium) of akinetic segments was 78% and was similar to LGE-MR (87%, p—NS). Specificity of MCE was higher than for LGE-CMR (72%, and 52%, respectively; p b 0.01). This pilot study has showed good diagnostic accuracy of MCE for prediction of function recovery after bypass surgery, which is comparable to “gold standard” in assessing myocardial viability — LGE-MR. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Hibernating myocardium; Contrast echocardiography; Magnetic resonance

Detecting viable but dysfunctional myocardium, whether stunned or hibernating, is critical to management of patients with coronary artery disease (CAD) because successful revascularization in such cases improves left ventricle (LV) function and prognosis [1–3]. Recently, several studies have shown that myocardial contrast echocardiography (MCE) enables assessment of myocardial perfusion and has the potential to predict recovery of function in patients shortly after acute myocardial infarction (AMI) [4–11]. However, there are still a few data about the accuracy of MCE in predicting hibernating myocardium. Aims of this pilot study were ☆

This work was supported by a grant from Czech Cardiac Society and by the Charles University Prague Research Project no. MSM 0021620817 awarded by the Ministry of Education, Youth and Physical Education of the Czech Republic. ⁎ Corresponding author. Tel./fax: +420 267162621. E-mail address: [email protected] (P. Tousek). 0167-5273/$ - see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2007.05.113

twofold: firstly, using rest intravenous MCE predict recovery of regional function in patients with ischemic LV dysfunction undergoing bypass surgery; secondly, to compare the accuracy of MCE with LGE-MR in this clinical setting. The study population consisted of patients with chronic, stable ischemic heart disease and severely reduced left ventricle function (EF b 40%) who were already indicated for coronary artery bypass surgery. Patients with severe valvular heart disease, patients undergoing other surgical operative procedures such as aneurysmectomy or mitral valve repair were not included. Conventional two-dimensional (2D) echocardiography, MCE and LGE-CMR were performed 1 to 10 days before bypass surgery. Patients underwent repeat 2D echocardiography 6 months after surgery to assess recovery of function. Regional wall motion was assessed during 2D echocardiography at rest and follow-up according to the 16-segment model of the American Society of Echocardiography [12] and graded semi-quantitatively as 1, normal; 2, hypokinetic;

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Table 1 Accuracy of MCE and LGE-MR in prediction of myocardial function recovery after bypass surgery Sensitivity, %

MCE preserved perfusion (grade 1 + 2) LGE-MR viable myocardium (grade 1 + 2)

Specificity, %

All dysfunctional segments

Akinetic segments

All dysfunctional segments

Akinetic segments

87 91

78 88

42 35

72 ⁎ 52

⁎ p b 0.01 vs LGE-MR.

or 3, akinetic. Myocardial segments were matched to coronary distributions as previously described [13]. Harmonic Power Doppler imaging was used for MCE at the same echocardiographic machine. Continuous intravenous infusion of Optison contrast agent (Amersham Health, Oslo, Norway) was administered using an infusion mixing pump SP-UPT1 (AVCR, Brno, Czech Republic). Each of the 16 segments was analyzed semi-quantitatively according to the intensity of the myocardial opacification as follows: 1, normal; 2, patchy; 3, absent.

Hyperenhancement (HE) in late gadolinium-enhanced images was also assessed in the 16-segment model comparable to that for echocardiography was used. According to the transmural extent of HE segments were graded as: 1, no HE; 2, HE b 50% of myocardial wall; and 3, HE N 50% of the myocardial wall. Segments with grade 1 or 2 were classified as viable myocardium. In this pilot study, 26 patients were eligible for MCE analysis and underwent 6-months follow-up. Fifteen patients underwent also LGE-MR. A total of 356 segments have been

Fig. 1. MCE and LGE-MR in a patient with history of inferior QIM. Upper line, 4-chamber (panel A) and 2-chamber view (panel B) of the LV during MCE, arrows indicate absent perfusion of lateral and inferior wall. Lower line, corresponding LGE-MR images. Extent of the hyperenhancement of the lateral wall does not exceed 50% of the myocardium (panel C), inferior wall is not viable (panel D).

P. Tousek et al. / International Journal of Cardiology 128 (2008) 117–120

revascularized, 282 (79%) of which were preoperatively dysfunctional. Hundred twenty seven (45%) preoperatively dysfunctional segments recovered function at 6-months follow-up. We could reliably assess myocardial perfusion in 326 (92%) of 356 revascularized segments. 30 segments were excluded due to bad visualization during MCE or artefacts. Preserved perfusion during MCE (grade 1 + 2) was detected in 89 (52%) from 170 akinetic segments. From these 89 akinetic segments with preserved perfusion, myocardial function recovered at follow-up in 64 (72%) segments. We assessed myocardial viability status using LGE-MR in 151 revascularized segments, 101 of which showed wall motion abnormality during preoperative echocardiography. 51 (64%) of 80 akinetic segments were classified during LGE-MR as viable myocardium. Only 26 of these segments recovered their function at follow-up (p ≤ 0.01 vs MCE). Diagnostic accuracy of both methods is shown in Table 1. The interobserver agreement for differentiation of normal, patchy and absent MCE opacification was 90% (κ = 0.79), and for differentiation of 3 grades of LGE-MR hyperenhancement was then 94% (κ = 0.84). Intraobserver agreement was 92% (κ = 0.84) for MCE image analysis and 95% (κ = 0.84) for LGE-MR. The present pilot study demonstrates that in patients with chronic CAD and LV dysfunction, MCE can be used for prediction of regional LV function recovery after bypass surgery. We have also compared for the first time MCE and LGE-MR in this clinical setting. Prediction of function recovery in segments with severe wall motion abnormality with MCE has a similar sensitivity but higher specificity compared with LGE-MR (Fig. 1). Until this time, few studies have studied the role of MCE in myocardial hibernation. A decade after the studies of deFilipi et al. [14] and Nagueh et al. [15] with intracoronary injection of contrast agent, Shimoni et al. have first evaluated hibernating myocardium using intravenous administration of contrast agent [16]. In their study, diagnostic accuracy of MCE was better using qualitative compared to semiquantitative assessment of myocardial perfusion. Sensitivity and specificity of MCE for prediction of recovery of akinetic segments were then 88% and 73%, respectively. However, quantification of MCE images needs off-line process and is very time-consuming. Therefore, we decided to use semiquantitative assessment of myocardial perfusion to bring this study near to clinical practice. We reached similar results in detecting hibernating myocardium in all dysfunctional segments as Shimoni, but we showed better accuracy of MCE in predicting recovery of function in akinetic segments. We are convinced that evaluation of viability in segments with severe wall motion abnormality has the biggest value. Majority of hypokinetic segments have preserved myocardial perfusion, at least in epicardial layers, and recovery of function or preservation of their geometry can be expected. The difference in prediction of function recovery between MCE and LGE-MR can be explained by relatively wide threshold for indicating viable myocardium during LGE-MR.

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The region of the myocardium, where the extent necrotic tissue is little less than 50% of myocardial wall, can be on one hand classified as viable myocardium, but on the other hand this myocardium does not have potential for function recovery. In conclusion, we have demonstrated that MCE has good diagnostic accuracy for prediction of function recovery after bypass surgery. We have further shown that in this clinical setting, MCE as a practicable bedside technique is comparable to not readily available “gold standard” in assessing myocardial viability — LGE-MR. On the basis of the present data, it appears reasonable to evaluate the role of MCE for risk stratification before bypass surgery in future studies in a larger cohort of patients. References [1] Haas MDF, Haehnel MDM, Christoph J, et al. Preoperative positron emission tomographic viability assessment and perioperative and postoperative risk in patients with advanced ischemic heart disease. J Am Coll Cardiol 1997;30:1693–700. [2] Pagley PR, Beller GA, Watson DD, et al. Improved outcome after coronary bypass surgery in patients with ischemic cardiomyopathy and residual myocardial viability. Circulation 1997;96:793–800. [3] Bax JJ, Poldermans D, Elhendy A, et al. Improvement of left ventricular ejection fraction, heart failure symptoms and prognosis after revascularization in patients with chronic coronary artery disease and viable myocardium detected by dobutamine stress echocardiography. J Am Coll Cardiol 1999;34:163–9. [4] Greaves K, Dixon SR, Fejka M, et al. Myocardial contrast echocardiography is superior to other known modalities for assessing myocardial reperfusion after acute myocardial infarction. Heart 2003;89:139–44. [5] Korosoglou G, Hansen A, Hoffend J, et al. Comparison of real-time myocardial contrast echocardiography for the assessment of myocardial viability with fluorodeoxyglucose-18 positron emission tomography and dobutamine stress echocardiography. Am J Cardiol 2004;94(5):570–6. [6] Hillis GS, Mulvagh SL, Gunda M, et al. Contrast echocardiography using intravenous octafluoropropane and real-time perfusion imaging predicts functional recovery after acute myocardial infarction. J Am Soc Echocardiogr 2003;16:638–45. [7] Lepper W, Sieswerda G, Vanoverschelde JL, et al. Predictive value of markers of myocardial reperfusion in acute myocardial infarction for follow-up left ventricular function. Am J Cardiol 2001;88:1358–68. [8] Main ML, Magalski A, Chee NK, et al. Full-motion pulse inversion power Doppler contrast echocardiography differentiates stunning from necrosis and predicts recovery of left ventricular function after acute myocardial infarction. J Am Coll Cardiol 2001;38:1390–4. [9] Main ML, Magalski A, Morris BA, et al. Combined assessment of microvascular integrity and contractile reserve improves differentiation of stunning and necrosis after acute anterior wall myocardial infarction. J Am Coll Cardiol 2002;40:1079–84. [10] Tousek P, Orban M, Swaiger M, Firschke C. Assessment of infarcted myocardium with real-time myocardial contrast echocardiography. Comparison with 99m-Tc sestamibi SPECT. Heart 2005;91:1568–72. [11] Swinburn JM, Lahiri A, Senior R. Intravenous myocardial contrast echocardiography predicts recovery of dyskinetic myocardium early after acute myocardial infarction. J Am Coll Cardiol 2001;38:19–25. [12] Schiller NB, et al, for the American Society of Echocardiography Committee on Standards. Subcommittee on Quantification of TwoDimensional Echocardiograms: Recommendation for quantitation of the left ventricle by two-dimensional echocardiography. J Am Soc Echocardiogr 1989;2:358–67.

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