1. LV function and remodeling. 2. Contribution of myocardial ischemia due to CAD, and

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2 The clinical syndrome of heart failure in adults is commonly associated with the etiologies of ischemic and non-ischemic dilated cardiomyopathy, hypertrophic cardiomyopathy, hypertensive heart disease, and valvular heart disease. Common principles of assessment, that influence prognosis and therapy include the assessment of: 1. LV function and remodeling. 2. Contribution of myocardial ischemia due to CAD, and 3. Myocardial viability. 4. MIBG. 5. Imaging Myocyte Necrosis and Apoptosis: 6. Selection for CRT. 2

3 Importance of detecting CAD in CHF: CHF CAD Non-ischemic CM It is a critical early step in the management of heart failure pts coronary angiography or not. Coronary Artery Disease Large MI No other CAD Moderate/large MI Remote CAD No MI Extensive CAD LV Dysfunction No Ischemia LV Dysfunction ischemia / scar LV Dysfunction ischemia / hypernation CHF CHF CHF 3

4 Non-invasive imaging methods for assessment of CV disease: Echocardiography. Nuclear cardiology. CT. MRI. Hybrid techniques. Non-invasive imaging methods for assessment of CV disease Nuclear Techniques 4

5 MPI to detect CAD in CHF: Sensitivity (NPV = 100%) Excellent Specificity Modest ( by GS) 5

6 MPI to detect CAD in CHF: Pts with CAD Pts without CAD High Low summed stress score. (SSS) summed stress score (SSS) (Danias et al., 1998, Am J Cardiol.). MPI to detect CAD in CHF: i.e. if MPI normal or mildly abnormal in pt with CHF + LV dysfunction. Significant CAD is unlikely No need for coronary angio 6

7 Meta-analysis of literature Non-viability predominant Intermediate Risk of death, not affected by revascularization Preserved myocardial viability by Revascularization Risk of death (Allman et al., J Am Coll Cardiol, 2002) b) Nuclear Techniques: Techniques & protocols for assessing myocardial viability by SPECT technique: 1) 201 TI stress redistribution. 2) 201 TI stress Reinjection. 3) 201 TI stress Late redistribution (24-48 h). 4) 201 TI rest Redistribution. 7

8 5) 99 Tc- Labeled Isotopes: Similar to TI-201 for detecting improvement in regional function after revascularization (SPECT & Gated SPECT). 6) PET Imaging: Have better overall accuracy for predicting recovery of regional function after revascularization than do SPECT techniques ( 18 FDG mismatch). Image Interpretation for myocardial viability: Quantitative vs visual analysis (semiquantitative) Accounting for defect severity (several scoring systems). 8

9 PET Prognostic value of viability: Total amount of PET Perfusion metabolism mismatch correlated linearly and significantly with improvement in functional status after revascularization (r = 0.82, P < ). Di Carli et al.,

10 58 ys. old male, In 1999, sustained anterior MI. CABG was done at that time. Hypertensive and dyslipidemic. Chest pain + SOB Q-waves V 1 -V 3, III and av F Upper normal LVEDd, %EF: 47%, RWMs: Akinetic LV apex, Apical to mid-segment of IVS and LV inferior wall, Hyperkinetic basal segment of LV lateral wall. 10

11 99m Tc sestamibi SPECT during Stress & at Rest 99m Tc sestamibi SPECT during Stress & at Rest 11

12 99m Tc sestamibi SPECT & 18 F FDG PET at Rest 18 F FDG gated-pet at Rest 12

13 Comparison of Mean ECG-gated FDG PET ventricular function measures in patients with and without events. No event Events P value (n = 69) (n = 21) EF 27%+8% 25%+7% 0.27 EDV ml ml ESV ml ml Stroke volume ml ml LV mass g g PET Incremental prognostic value of LV functional parameters (LVEDV). (Santana et al., 2006) 13

14 Incremental value (defined as Δ x 2 statistic) of LV volumes over and above clinical history and PET mismatch data. (Santana et al., 2006) MIBG: Analog of false neurotransmitter guanethidine Adrenergic nerve terminals (similar to norepinephrine) Imaging of adrenergic nerve terminals (in heart & other tissues) Tagging with I-123 Planar or SPECT imaging Non-invasive in vivo visualization of adreno-receptor density in CHF, post MI, post-transplant 14

15 MIBG: a) In ischemic CM: Significant in MIBG uptake in areas of MI (acute & chronic ischemia). Area of sympathetic nerve damage is larger than area of myocardial necrosis (perfusion / innervation mismatch). Denervated but viable myocardium substrate for ventricular arrhythmia in pts with CAD. MIBG: b) In DCM: MIBG uptake ( b-adrenoreceptor density) MIBG washout ( adrenergic tone). H/M ratio correlated with LVEF (the lowest MIBG uptake in pts with lowest LVEF). H/M ratio plasma norepinephrine. (Schrofer et al., 1988) 15

16 MIBG: MIBG washout correlated with worsening NYHA functional class & plasma norepinephrine. In dilated (non-ischemic) CM uptake. diffuse in MIBG In ischemic CM heterogeneous MIBG uptake. MIBG washout in both dilated and ischemic CM. Survival rates based on an index of cardiac MIBG uptake (H/M ratio) Survival rates based on LVEF. 16

17 MIBG: Tracking response to medical treatment: ACEI & b-blockers Improve morbidity & mortality in pts with CHF. Improve MIBG uptake & washout. NYHA class. MIBG: Abnormalities in MIBG imaging potent prognostic value in pts with CHF (ischemic non ischemic). Viable but abnormally innervated myocardial tissues risk of ventricular arrhythmia. MIBG imaging identify high risk pts or low risk pts for sudden cardiac death. 17

18 MIBG: Recently, ICD implantation in asymptomatic ischemic CM pts with LVEF < 30% mortality benefit (MADIT II). i.e. MIBG imaging has a potential role, in determining pts at high risk for sudden death ICD. Imaging Myocyte Necrosis and Apoptosis: Antimyocin Antibodies Myocardial Damage. In acute MI, myocarditis, DCM, drug induced CM, allograft rejection. Annexin V imaging Apoptosis open the way to: 1- Newer forms of evaluation in CHF. 2- Risk stratification of DCM & HTN. 3- Evaluation of therapy. 18

19 Advantages of nuclear cardiology: A. Stress/Rest MPI (in contrast to stress echo highly stranderdized (acquizition, processing, interpretation & reporting (ASNC effort). B. Objective interpretation a strength that echo, other imaging techniques have not begun to manifest. C. - Operator independent. - Quantitative assessment. Advantages of nuclear cardiology: Cardiac PET: V. high sensitivity & specificity. Quantification of absolute coronary blood flow & flow reserve. Rubidium 82 generator No need for cyclotron. FDG viability. Limitations: Expensive, tracer cost. 19

20 Cardiac resynchronization therapy (CRT) is approved for the treatment of patients with advanced heart failure (HF) symptoms. LVEF < 35 and wide QRS (> 120 ms) 20

21 CRT was approved by the FDA in 2001 based on the MUSTIC and the MIRACLE trials. In patients with end-stage HF, depressed LVEF and wide QRS (>120 ms). 20% to 30% of these patients do not respond to CRT. 30% of patients with a wide QRS complex (>120 ms) do not have substantial LV dyssynchrony on echocardiography one third of patients with a narrow QRS appear to have substantial LV dyssynchrony on echocardiography Results of the PROSPECT trial showed that TDI and myocardial strain-rate is not ready for routine clinical evaluation of LV dyssynchrony. 21

22 Time when the electrical wave of activation reaches the contractile segment (electrical) Time when the contractile segment starts to thicken (mechanical) Time when the corresponding endocardial segment starts to move inward (mechanical) In dyssynchrony electrical activation is not necessarily equal to mechanical activation 22

23 Chen et al, JNC 2005;12:

24 Patient in HF NYHA Class III or IV? LVEF < 35%? LV dyssynchronous? QRS > 130 ms (electrically). Mechanically (accurately and reproducibly). Is lateral wall infarcted? Usual placement for 3rd lead. Bleeker et al, Circulation 2006; 113:

25 A female patient had class-iii HF due to dilated cardiomyopathy and left bundle branch block. She improved to class-i HF after CRT. Pre CRT Post CRT Normal Limits Phase SD 68.9o (*P < ) 14.4 o (* P = ) o Bandwidth 211o (* P < ) 46 o (* P = ) o *One-sample z test Ami E. Iskandrian, MD, University of Alabama at Birmingham 25

26 Processing is automatic and may be applied to previous acquisitions. Uses synchronicity and viability information to predict which patient will respond to CRT. 26

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39 Conclusion Nuclear cardiology is applicable tool in detection of viability, inflammation and can evaluate different therapeutic strategies in heart failure. We Still need to find the best predictor model for myocardial recovery after revascularization however careful interpretration of myocardial perfusion serve as an important guide. 39

40 Thank You 40