DISCLOSURES - Honorarium – Research / Advisor, Expert Services and Conferences in Nuclear Cardiology

BMS, CVT, Astellas, Lantheus, PGx Health, International Atomic Energy Agency

Royalties – Publications in Nuclear Cardiology Springer-Verlag-Nuclear Cardiology and Correlative Imaging: a teaching file, NY, 2004 Lippincott Williams & Wilkins, - Nuclear Medicine teaching File, 2009

João V. Vitola

Quanta Diagnostico Nuclear

Brazil

Viability by SPECT

65 yo male Atypical chest pain No history of CAD/MI HTN, hypercholesterolemia

Vitola and Delbeke: Nuclear Cardiology and Correlative Imaging, Springer 2004, NY, Chapter 3

Case

SAV – EXERCISE SAV - REST

VLA – EXERCISE VLA - REST

HLA – EXERCISE HLA - REST

1- Does the ECG change represents a silent MI in the past ? 2- Does he need any additional viability study ?

Myocardial Viability: 99mTc-perfusion agents

• Retention of MIBI and tetrofosmin depends on cell membrane integrity and mitochondrial function.

• 99mTc-perfusion agents do not redistribute and may underestimate viability compared to 201Tl or FDG

• Improvement for detection of viability with quantitative SPECT criteria and nitrate administration

Cuocolo A et al. J Nucl Med 1992;33:505-51 Soufer R et al. Am J Cardiol 1995;75:1214-1 Altehoefer C et al. J Nucl Med 1994;35:569-

Conclusions • TMT was less sensitive than MPI for LCX

ischemia detection • CAD and prior MI detected in a patient with no

history • MIBI was consistent with rest ECG, confirming

the suspicion of a prior silent MI • MIBI detected a large area of viable tissue at

risk, not requiring any other test to decide management

• MIBI can be used as a viability agent, however underestimation of viable tissue may occur in some cases and further testing may be needed

Case • 68 year-old woman with a history of

silent inferior MI who presented with episodes of atrial fibrillation and ventricular tachycardia

• ECG: – Q waves in II, III, AVF

• Coronary angiography: – Occluded RCA with collaterals to the distal

inferior wall from the left circulation

Rest only - 15 min Rest- 4h redistribution 201Tl

Membrane Integrity: Thallium-201 • Analog of potassium

– Myocardial extraction by active and passive transport

– High first pass uptake – 89% – Myocardial localization: 4% injected dose

• Does redistribute according to perfusion • Allows evaluation of perfusion and cell

membrane integrity (a requirement for viability)

Vitola and Delbeke: Nuclear Cardiology and Correlative Imaging, Springer 2004, NY, Chapters 3 and 8

Membrane Integrity: 201Thallium SPECT Rest-4h redistribution - Semiquantitation

• Patterns of uptake in dysfunctional myocardium: – Fixed defect: <50% of normal:

transmural scar – Fixed defect: 50-80% of normal: non-

transmural scar – Redistribution – Myocardium at risk -

viable

Bax JJ et al. Eur J Nucl Med 1997;24:516-522.

Membrane Integrity: 201Thallium SPECT • Stress/Rest imaging

– 4-hour redistribution imaging: • fixed defect frequently viable: 45% of fixed

defects improve after revascularization.

– Resting imaging after reinjection of 201Tl improves viability assessment : 30-50% fixed defects at 4h redistribution show reversibility.

– 24-h redistribution imaging (in average additional 6%)

Kiat H et al. JACC 1988;12:1456-1463. Yang LD et al. JACC 1990;15:334-340. Dilsizian V et al. NEJM 1990;323:141-146.

Value of 24h imaging: Small number of patients:

– Up to 30% of patients with fixed defects (rest-4 hrs) will show improved uptake at 24h

– But only 3% of patients with fixed defects of <50% uptake of normal

Membrane Integrity: 201Thallium SPECT

Wagdy HM et al. Nucl Med Commun 2002;23:629-637. Matsunari I et al. J Nucl Med 1997;38:1073-1078.

Does a Fixed Defect on Rest / Stress Tc-99m Sestamibi Study Underestimate Myocardial

Ischaemia?

Comparison with 24 Hr Tl-201 Study with Short-term follow-

up

Dr G. Kong, Dr D. Gunawardana, Dr M. Lichtenstein, Dr K. Roysri, Dr N. Better,

Dr D. Sivaratnam

Nuclear Medicine Department, The Royal Melbourne Hospital, Grattan Street, Parkville, Victoria.

Clin Nuc Med ….March 2008

Methods • Prospective study • 50 consecutive pts • Accrued March 2005 – July 2005

• Patients with

– Fixed defects on MIBI – High clinical suspicion of reversible ischemia

•Received additional thallium study

Endpoints

3 and 6 months post-scan 1. Acute myocardial infarction (AMI) 2. Unstable angina requiring admission 3. Cardiac Intervention (CABG / PCI) 4. Cardiac Death • Medical records / Treating physician

Tl reversibility

69% (34/49) with fixed MIBI defects showed additional reversibility

Number of patients

Total 49

No reversibility 15 (31%)

Reversibility 34 (69%)

Case MIBI: Fixed inferior, lateral and antero-lateral wall defects

Delayed Tl: Significant reversibility

Cardiac Events 6 months

n = 1 AMI n = 4 USA (3 PCI) n = 6 3 CABG 3 PCI No Cardiac Deaths

P = 0.027

32%

11/34

1/15

• 61 yo man with exercise induced chest pain (typical angina) • AMI 2 1/2 y ago, followed by CABG: LIMA to LAD and SVG to the LCX

• Last cath 6 mo ago: 99% native LAD, occluded LIMA, antero-apical akinesia

•Meds: Carvedilol, ACEI, nitrate, ASA, Statin and Aldactone

Referred for a SESTAMIBI study

•MPI: Bruce, 10 METS, ECG positive – new ST depression 1 mm, denied chest pain

Case

Stress/Rest MIBI • Hx of exercise induced chest pain + new ST depression 1 mm om TMT

Stress/Rest MIBI

•exercise induced chest pain, new ST depression

Next Step ?

Nitrate administration

Venodilation Preload reduction

Decrease of LV volume and wall stress Reduction of myocardial oxygen demand

Coronary blood flow redistribution towards ischemic regions by reduction of LV end-diastolic pressure

Nitrate Myocardial Perfusion Imaging

0 5 10 15 20 25 30 50 70

SPECT imaging

Nitrateadministration

Tracerinjection

Resting conditions

Time (min)

MIBI with nitroglycerin (NTG)

Scar > Ischemia MIBI without NTG

Ischemia > Scar MIBI with NTG

STRESS

STRESS

REST

STRESS

REST

STRESS

REST

•exercise induced chest pain, new ST depression

Next Step : nitrate MIBI = good choice

REST

Rest without NTG Rest with NTG

STRESS STRESS

REST REST

Akinetic antero - apical region

Case

• 52 year-old man with CHF and global LV dysfunction on echocardiography

• Coronary angiography: severe 3-vessel CAD

• Nitrate: How does it work? – Preload reduction, some dilatation of stenotic epicardial

vessel and improvement of collateral circulation • How to administer?

– 0.4-0.8 mg sublingually 5 -10 min before the radiopharmaceutical

• Can be used with 201Tl or 99mTc-perfusion agents • Performance?

Myocardial Viability Resting and nitrate-enhanced SPECT

Bisi G et al. JACC 1994;24:1282-1289. Batista JF et al. J Nucl Cardiol 1999;6:480-486. Oudiz RJ et al. Am Heart J 1999;138:206-209.

FDG

Viable Necrotic

Via

ble 75

(57%)34

(26%)

3(2%)

Nec

rotic 19(15%)

Baseline Tetrofosmin

Agreement: 94/131 (72%)Kappa = 0.35

Nitrate Tetrofosmin

FDG

Viable Necrotic

Via

ble 89

(68%)20

(15%)

3(2%)

Nec

rotic 19

(15%)

Agreement: 109/131 (82%)Kappa = 0.53

Cardiac Tomography After Nitrate Administration in Patients With Ischemic LV Dysfunction: Relation to Metabolic Imaging by PET

He W, et al. J Nucl Cardiol 2003

Cardiac Tomography After Nitrate Administration in Patients With Ischemic LV Dysfunction: Relation to Metabolic Imaging

by PET

He W, et al. J Nucl Cardiol 2003

Patient 1 Patient 2

69

8681 86

0

20

40

60

80

100

Sensitivity SpecificityHe W, et al. J Nucl Cardiol 2003

Per

cent Baseline

Nitrate

Sensitivity and Specificity of Baseline and Nitrate Tetrofosmin SPECT for Detecting Preserved Metabolic Activity in Patients With Ischemic LV Dysfunction

p < 0.01 p = NS

Detection of Myocardial Viability by Radionuclide Imaging Gold Standard: Recovery of LV Function

90 8681

91 92

54

6760

88

73

0

20

40

60

80

100

Tl-201 Red Tl-201 Rein Mibi Mibi-Nitrate FDG-PETBax et al. J Am Coll Cardiol 1997

%

Sensitivity Specificity

Stunning

Scar from prior MI

Hibernation

Subendocardium 20-30 % = akinesia May have lots of viable tissue

Chronic cases = Mixed pattern

Lieberman AN et al, Circulation 1981;63:739-746

Contribution of the subendocardium to contractility

Akinetic anterior wall

Pooled Data from Studies Focusing on Prediction of Recovery of Function Post-revascularization

Technique #Studies/ patients

Sensitivity Specificity NPV PPV

FDG PET 20/598 93% 58% 86% 71%

201Tl 33/858 87% 55% 81% 64%

99mTc-tracers 20/488 81% 66% 77% 71%

Dobutamine Echo/MRI

32/1090 81% 80% 85% 77%

Pooled data 105/3034 84% 69%

Bax JJ et al. Curr Probl Cardiol 2001;26:142-186

Why is nuclear less specific compared to echo for Fx improvement ?

Qureshi U et al. Circulation 1997;95:626-635

Subendocardium MI may lead to akinesia Akinetic segments may have lots of viable tissue detected by Nuclear Scar may prevent improvement of function and detection by echo

• FDG is taken up by viable myocardial regions even when flow is significantly reduced.

• Effectively differentiates nontransmural MI from hibernating condition.

• Soft tissue attenuation correction is routinely performed.

PET FDG for Viability Assessment Advantages over SPECT

• PET FDG is the preferred imaging method for assessment of myocardial viability.

• If SPECT is done first, PET should be considered in those with non- or partially reversible defects.

PET vs. SPECT for Viability Assessment

Conclusions

• MIBI can be used as a viability agent, however underestimation of viable tissue may occur and further testing may be needed in special cases

• Nitrates are easy and safe to use and increase the sensitivity of rest MIBI to detect viable tissue

• There are data in the literature supporting the use of Nitrate MPI with similar accuracy to other protocols including thallium and FDG (LV Fx dependent)

• Akinetic areas may be present after a subendocardium MI

• Viability studies may show large quantities of viable tissue at risk in akinetic areas