Zahid Rahman Khan, MD(USA), MS Diplomate American Board of Nuclear Medicine Consultant t Nuclear Medicine

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Zahid Rahman Khan, MD(USA), MS Diplomate American Board of Nuclear Medicine Consultant t Nuclear Medicine i North West Armed Forces Hospital Tabuk, KSA. 1

Introduction Hibernation: Term coined by Rahimtoola 1. Chronically ischemic myocardium with decreased blood flow & down regulation of contractility; reversible with blood flow restoration 2. Meta-analysis 3088 patients(24 studies), annual mortality with viability was 16% with medical tx & 3.3% with revascularization (p<0.0001) 0001) 3. 1. Barrington SF. Left ventricular dysfunction. In: Cook CRJ, Maisey MN, Britton KE, Chengazi V. Clinical Nuclear Medicine. 4 th edition. London: Hodder Arnold; 2006:183-194. 2. Ziessman HA, O Malley JP, Thrall JH. Cardiac System. In: Ziessman HA, O Malley JP, Thrall JH. Nuclear Medicine The Requisites. 3rd edition. Philadelphia: Mosby; 2006:450-507. 3. Allman et al. Myocardial viability testing & impact of revascularization on prognosis in patients with CAD & LVD: a metaanalysis. J Am Coll Cardiol 2000;39:1151-8. 3 Introduction The role of MIBI is well established in detection of severely ischemic but viable myocardium 1. Used alone Tc-99m MIBI may underestimate the viable myocardium 2,3. Nitrates have been used to augment uptake of Tc tracers. It dilates epicardial vessels and flow through collateral vessels increase 4. 1. Bono RO, Dilsizian V. Thalium-201 and Tc-99m MIBI for assessing voable myocardium. J Nucl Med 1992; 33:815-18. 2. Maurea S, Cuocolo A, Pace L, Nappi A, Imbriaco M, Morisco C, et al. Rest injected Thalium 201 redistribution and resting Tc-99m sestamibi uptake in coronary heart disease. Eur J of Nucl Med; 1993;20:502-.10. 3. Marzullo P, Sambuceti G, Parodi O. The role of sestamibi scintigraphy in the radioisotopic assessment of myocardial viability. J Nucl Med 1992;33:1925-30. 4. He Z, Verani MS. Evaluation of myocardial viability by myocardial perfusion imaging: should nitrates be used? J of Nucl Cardiology 1998;5:527-32. 4 2

Diagnostic techniques Myocardial Metabolism: PET (FDG)- Gold standard. Cell membrane integrity: Rb & Tl-201. Cellular metabolism: 99m Tc-MIBI & 99m Tc-tetrophosmine (Nitrates/trimetazidine enhanced). Contractility: LDD Echo & LDD MRI. Microvascular damage: Delayed enhancement MRI. Barrington SF. Left ventricular dysfunction. In: Cook CRJ, Maisey MN, Britton KE, Chengazi V. Clinical Nuclear Medicine. 4 th edition. London: Hodder Arnold; 2006:183-194. 5 SPECT imaging withtc-99m MIBI Diffuses across cell membrane & sequestered in mitochondria. Retention dependent on cell membrane integrity & mitochondrial function (depends on active metabolism) 1. For hibernating myocardium Sensitivity (rest) : 80%, Specificity: 60-70% 2. With nitrate Sensitivity :77-95%, Specificity: 69-88% in small groups of patients 3. 1. Barrington SF. Left ventricular dysfunction. In: Cook CRJ, Maisey MN, Britton KE, Chengazi V. Clinical Nuclear Medicine. 4 th edition. London: Hodder Arnold; 2006:183-194. 2. Bax JJ, et al. J Am Coll Cardiol1997;30:1451-60, Wijns W, et al. N Engl J Med 1998;339:173-81. 3. Bisi G, et al. J Am Coll of Cardiol 1994;24:1282-9, Sciagra R, et al. Eur J Nucl Med 2001;28:680-7., Maurea S, et al. J Nucl Med 1995;36:1945-52, Li ST et al. J Nucl Cardiol 1996;3(6 Pt 1):457-63. 6 3

Aims and Objectives of the study To assess myocardial viability with nitrate enhanced Tc- 99m sestamibi Gated Single Photon Emission Computed Tomography (GSPECT) in patients with coronary artery disease. 7 Materials and Methods A prospective study of 48 patients with known CAD & history of myocardial infarction was done from Jan 2009 to Jan 2010. Inclusion criteria 1. Consecutive patients referred to Nuclear Cardiology section of Lady Reading Hospital Peshawar, Pakistan. 2. History of MI. Exclusion criteria 1. Hypotension. 8 4

Materials and Methods 99m Tc-MIBI Gated SPECT: 1. Patient preparation: - Through explanation of procedure - H & P examination using a comprehensive proforma - Informed consent. 2. Pre-procedure pertinent information: - Fasting for at least 4 hours. 3. Dose: - 925-1,110 MBq (25-30mCi) 99m Tc-MIBI, Intravenously. - Medi-MIBI 500µgm kit from Hungary was used. Image : Abdel-Dayem H M. practical demonstration: scintimammography procedures. St. Vincents Hospital and Medical Center,, New York Medical College, Valhalla, New York 9 Materials and methods 4. Instrumentation: - Large FOV Siemens gamma camera - ecam signature series single head system with LEHR collimator. - Symmetric 15% energy window centered over the 140kev photopeak. 5. Patient position: - Supine. 10 5

Materials and methods 6. Imaging protocol (Two-day): - Baseline study: RP @ rest and image acquisition iti @ 30-60min - Nitrate study: Sublingual nitrates (1-2 tablets) & RP after 15 minutes. Image acquisition @ 30-60 minutes. Nitrate RP INJECTION 15 min 60 min Gated SPECT 11 Materials and methods 7. Image processing: - Data processing Syngo 2007A software. - Manual reconstruction & Butterworth filter applied. - Short axis, vertical long axis and horizontal long axial slices obtained. - Quantification & gated image acquisition- Corridor4DM v5.1 soft ware applied. 12 6

Materials and methods Image interpretation of Tc-99m GSPECT: - Two independent observers interpreted the studies. - Conventional slice display of SPECT images was done. - Perfusion defect severity & extent evaluated with Semiquantification method using 20 segment model. - Gated imaging quantified with Corridor4DM v5.1 software. Statistical analysis: - Paired t test. 13 Results Total of 48 patients (age range 24-82 years) were included. 39 males, 9 females. 90 80 70 960 segments evaluated 40 A 30 LAD:480, g e 20 RCA:192, 10 0 LCx: 288. 60 50 1 4 7 10131619222528313437404346 Series1 14 7

Results Comparison of SPECT baseline and Nitrate enhanced study Territory segments Baseline study Nitrate study %age P valve (viable (viable improvement segments) segments) of viability with nitrates LAD 480 244 276 13.11% <0.01 RCA 192 148 153 3.38% 0.096 LCx 288 206 241 16.99% <0.01 Total 960 598 670 12.04% <0.01 15 Results Gated study information for both rest and nitrate t enhanced study was also assessed for same 48 patients. For gated study total segments evaluated were 960 (LAD: 480, RCA: 192 & LCx: 288). 16 8

Results Comparison of Gated baseline & Nitrate enhanced study Territory segments Gated Gated Nitrate %age Pvalve Baseline study (viable improvement study (viable segments) of viability segments) with nitrates LAD 480 224 240 7.14% 0.16 RCA 192 125 120-0.4 LCx 288 244 245 0.41% 0.86 Total 960 593 605 2.02 0.39 17 Results Comparison of (SPECT + Gated) baseline & (SPECT + Gated) Nitrate t enhanced study Territory p value LAD 0.001 RCA 1 LCx 0.001 Total 0.001 18 9

Results Gated image acquisition in addition to SPECT: - P value was not significant when gated rest and gated nitrate study was compared. - But combination of both (SPECT+ Gated) baseline & (SPECT + Gated) nitrate t enhanced showed significant p value (0.001). 19 20 10

21 22 11

Results 23 Results 24 12

25 26 13

27 28 14

29 30 15

31 32 16

Literature Review Niyaz K, et al. 35 patients (31 M, 4F) hx of MI. Baseline and NTG Tc-99m MIBI (2 day protocol). 15 had Rest/redistribution Tl-201(3 day protocol). Images divided into seven segments for qualitative & semiquantitative analysis. > 55% tracer activity compared to max - viable. Niyaz K, et al.assessment of Viable Myocardium by Nitrate Augmented 99m Tc MIBI Myocardial Perfusion Imaging. JPMA 57:83;2007. 33 Literature Review Baseline 168/245 (68.57%) viable, to 197 (80.40%) in Nitrate MIBI (p=0.001 vs baseline). Concordance of viable segments detection between NTG MIBI & redistribution Tl-201 found in 100/105 segments (95.24%) for 15 pts. Nitrate MIBI SPECT results in improved detection of viable segments & achieves results similar to Tl rest/redistribution. Niyaz K, et al.assessment of Viable Myocardium by Nitrate Augmented 99m Tc MIBI Myocardial Perfusion Imaging. JPMA 57:83;2007. 34 17

Literature Review Galli et al 54% patients showed significant decrease in mean perfusion defect after sublingual NTG 1. Maurea et al 27% perfusion defects showed improvement after NTG 2. 1. Galli M, Marcassa C, Imperato A et al. Effects of nitrogylcerine technitium- 99m sestamibi tomoscintigraphy on resting global myocardial hypoperfusion in stable patients with healed myocardial infarction. Am J Cardiol1994;74:843-48. 2. Maurea S, Cuocolo A, Soricelli A et al. Enhanced dectection of viable myocardium by Tc-99m MIBI imaging after nitrate administration in chronic coronary artery disease. J Nucle med 1995;36:1945-52. 35 Limitations 1. Lack of Positron emission tomography or thalium-201 for comparison. 2. Need of follow-up studies to see the effect of revascularization. 3. Better attenuation correction. 36 18

Conclusion Nitrate augmented Tc-99m sestamibi myocardial SPECT significantly improves detection of viable (Hibernating) myocardium. Gated images may further improve the accuracy of detection of hibernating myocardium in borderline cases. 37 38 19

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