1. Dysfunctional but viable myocardium Ischemic heart disease assessed by MRI and SPECT Martin Ugander, MD Department of Clinical Sciences, Lund Department of Clinical Physiology Lund University

2. Supervisor:Håkan Arheden, MD, PhD Clinical Physiology, Lund Co-supervisor:Peter Cain, MBBS, PhD Wesley Heart Clinic, Brisbane, AU Funding: Swedish Research Council Swedish Heart Lung Foundation Faculty of Medicine at Lund University Region of Scania

3. Aim To further elucidate the pathophysiology of dysfunctional but viable myocardium in patients with ischemic heart disease.

4. Outline of Studies Study I- Method for quantitative MRI & SPECT Study II - Wall thickening vs. Infarct transmurality Study III - LVEF vs. Infarct size Study IV - Time course of perfusion & function after revascularization

5. Study I Quantitative polar representation of left ventricular myocardial perfusion, function and viability using SPECT and cardiac magnetic resonance: initial results Cain PA, Ugander M, Palmer J, Carlsson M, Heiberg E, Arheden H. Clin Physiol Funct Imag 2005 (25) 215-222

6. Background Clinical management of CAD involves complex assessment of the extent and severity of changes in function, perfusion and viability. No adequate research tools for quantitative assessment exist.

7. Aims To explore the feasibility of integrative quantitative representation of LV perfusion, function and viability in polar plots. To determine agreement between visual scoring and quantitative measures.

8. Methods 10 patients scheduled for CABG –rest/stress SPECT –Cine and delayed enhancment CMR Quantification with in-house software Comparison with visual scoring using Kendall’s coefficient of concordance (W)

9. Methods

11. Results

12. Kendall’s W: 1.0 (p<0.001)0.85 (p<0.001)

13. Conclusions Side-by-side quantitative polar representation of LV perfusion, function and viability is feasible and may aid in the complex assessment of these parameters. The agreement between quantitative measurement and visual scoring was very good.

14. Study II Infarct transmurality and adjacent segmental function as determinants of wall thickening in revascularized chronic ischemic heart disease Ugander M, Cain PA, Perron A, Hedström E, Arheden H. Clin Physiol Funct Imag 2005 (25) 209-214

15. Background Regional LV function in patients with IHD may be influenced by many factors.

16. Aims To explore how regional wall thickening in patients with chronic IHD is affected by both infarct transmurality and the function of adjacent segments. To compare with results from healthy subjects.

17. Methods 20 patients –6 months after revascularization –Cine CMR –Delayed enhancement CMR 20 matched controls –Cine CMR

22. Multivariate analysis of parameters contributing to wall thickening t p Infarct transmurality -4.5 <0.001 Number dysf. adjacent seg.-22.9 <0.001

23. Conclusion The number of dysfunctional adjacent segments is a greater determinant than infarct transmurality on regional wall thickening. Infarction is difficult to assess by resting function alone. DE CMR is an important tool in this setting.

24. Study III A maximum predicted left ventricular ejection fraction in relation to infarct size in patients with ischemic heart disease Ugander M, Ekmehag B, Arheden H. Submitted

25. Background An understanding of the relationship between LVEF and infarct size is important when assessing the potential benefit of revascularization in patients with IHD.

26. Aims To explore the relationship between LVEF and IS. To determine a maximum predicted LVEF for a given IS.

27. Methods 297 patients clinically referred for viability assessment by CMR LVEF Infarct size (% LVM)

28. Methods Infarct size (%LVM) LVEF (%) A θ B C

29. Patient characteristics (IHD)

30. Distribution of infarctions

31. Distribution of number of coronary artery vessel territories

32. Results

33. CineContrast LVEF=29%IS=36% 2ch 4ch

34. CineContrast LVEF=25%IS=6% 2ch 4ch

35. Conclusions LVEF cannot be used to estimate IS. IS cannot be used to estimate LVEF. LVEF can be used to estimate a maximum predicted IS. IS can be used to estimate a maximum predicted LVEF.

36. Study IV Influence of the presence of chronic non- transmural myocardial infarction on the time course of perfusion and functional recovery after revascularization. Ugander M, Cain PA, Johnsson P, Palmer J, Arheden H. Manuscript

37. Background The time course of recovery of LV function and perfusion after revascularization is not fully understood.

38. Aims To study the effect of presence of infarction on the time course of recovery of perfusion and function after elective revascularization.

39. Methods 15 patients (inclusion ongoing) –first time elective CABG (n=13) or PCI (n=2) Imaging –rest/stress SPECT –cine and delayed enhancement CMR –Before revasc., 1 & 6 months after revasc.

40. Patient characteristics 14 men, 1 woman mean age 68 years (range 52-84) 3VDn=6 2VDn=6 1VDn=3 LVEF = 49  10%

41. Distribution of infarct transmuralities

43. Conclusions Dysfunctional segments without infarction improved both perfusion and function at 1 month. Segments with infarction showed improved perfusion at 1 month and improved function at 6 months. This may reflect more severe ischemic burden in segments with infarction.

44. Summary Study I- Method for quantitative MRI & SPECT Study II - Wall thickening vs Infarct transmurality Study III - LVEF vs Infarct size Study IV - Time course of perfusion & function after CABG

45. Conclusion It is important to perform quantitative assessment of function,perfusion and viability in combination when studying the pathophysiology of dysfunctional but viable myocardium in IHD.

46. www.med.lu.se/cmr Martin Ugander, MD, PhD-student Ann-Helen Arvidsson, tech Erik Hedström, PhD Marcus Carlsson, MD, PhD-student Christel Carlander, tech Håkan Arheden, MD PhD Karin Markenroth, PhD Bo Hedén, MD PhD Henrik Engblom, MD, PhD-student Einar Heiberg,PhD Henrik Mosén, MD, PhD Erik Bergvall, MSc, PhD-student

48. The ischemic cascade

52. Mahrholdt et al 2005 Eur Heart J