Post on 31-Oct-2018
Cardiología Nuclear:
Evaluación de la inervación adrenérgica.
Papel de la gammagrafía con MIBG-I123 en el
manejo de pacientes con insuficiencia cardiaca.
Claudio Tinoco Mesquita
Claudio Tinoco Mesquita
Universidade Federal Fluminense
Professor de Medicina Clinica
Jefe Servicio Medicina Nuclear
Hospital Pró-Cardíaco
Jefe Servicio Medicina Nuclear
Cardiólogo y Medico Nuclear
Inervación Cardíaca
Autonomic
Innervation
of the Heart
Properties of Cardiac Autonomic System
Sympathetic System Parasympathetic System
Origin Intermediate horn of T3-T6 Brain stem via Vagus nerve
Distribution Atria and ventricles Predominantly in atria
Receptors Adrenoceptors: 1, 2 ,1, 2
Muscarinic receptors
Neurotransmitters Norepinephrine (major) Acetylcholine
Effects
Heart rate : Mainly 1, also some 2
Cardiac output
Contractility : Mainly 1, also some 2 (atria also)
Conduction : 1
Coronaries Dilation (2); constriction () Dilation
Lautamäki, Tipre, Bengel. Eur J Nucl Med Mol Imaging 2007;34:S74-S85.
Tyrosine
Dopa
Dopamine
Norepinephrine
PRESYNAPSE
POSTSYNAPSE
Axon
Myocyte
NE NE NE
NE
SYNAPTIC
CLEFT
1 1 2
NE
NE NE NE
NE Uptake 1
NE NE
Uptake 2
NE release into
synaptic space
Post synaptic receptors
G G
AC AMP cAMP
Vesicles
Sympathetic Neuron Synapse
NE
Norepinephrine Synaptic Cleft
Clearance
Uptake 1 Neuronal
92%
Uptake 2 Non-neuronal
4%
Circulation Spill Over
4%
Inervación en
la Falla Cardiaca
Down-Regulation
Norepinephrine Neuronal Transporter (NET)
Gene do NET: Braço longo do Cromossomo 16 (16q12.2)
HF
↑NE
↑ PKC
↓ NET
NE enzyme
oxidation
Increase in oxygen free
radicals production
↓ density NET Free radicals
bind to NET
NET Dysfunction
Chronic Heart Failure:
Increase in Autonomic Tonus and Reduction in
Receptor Density
123I-MIBG
Molecular Structures of Norepinephrine (NE), Guanethidine, and 123I-MIBG
No need to withdraw heart
failure medication for MIBG
Imaging.
123I-MIBG
MIBG IMAGING Parameters Assessed
Global cardiac uptake of tracer (planar, delayed images)
Heart/mediastinal ratio. 2.2 0.3 (<1.6 is 2 SD below normal mean).
Global washout (planar, from initial to delayed images)
Measures ability of myocardium to retain MIBG.
Normal pts: 10% 9%. Higher values correlate with disease, such as CHF. (>27%: dramatically increased mortality).
Regional uptake of tracer (SPECT)
Heterogeneous uptake may indicate regional denervation, i.e, autonomic imbalance, and possibly increased susceptibility to arrhythmia.
Hattori N, Schwaiger M. Eur J Nucl Med 2000;27:1-6. Flotats and Carrió. J Nucl Cardiol 2004; 11:587-602.
Ogita H, et al. Heart 2001; 86:656-660.
H/M ratio = 2.24
WO = 10.64
H/M ratio = 1.29
WO = 23.35
NORMAL ABNORMAL
LATE MIBG AND REST SESTAMIBI SPECT IMAGES
Potential Clinical Uses of MIBG
Congestive Heart Failure Prognosis
Assess response to standard medical therapy
Identify pts who would benefit from mechanical interventions (CRT, LVAD, Transplant)
Cardiac Arrhythmias Assess risk for sudden cardiac death
Better identify patients who would benefit from ICD
Assess patients with primary arrhythmias
Monitor recovery & complications post Cardiac Transplant
Assess patients with Ischemic Heart Disease Increased sensitivity to detect disease
Ischemic memory
Identify higher risk patients with Diabetes Mellitus
Assess toxic effects of Chemotherapy
MIBG en la Falla Cardíaca
Decrease in retention of MIBG:
Increase in Washout
123I-MIBG Imaging and Prognosis
in CHF/LV Dysfunction
0
20
40
60
80
100
120
0 5 10 15 20 25
ELAPSED TIME IN MONTHS
SURVIVAL RATE
(%)
H/M > 120%
H/M < 120%
p< 0.001
Merlet P et al. J Nucl M ed 1992.
90 pts. with CHF and EF < 45%
H/M 4 hrs after injection
123I-MIBG Imaging for Risk of Major Cardiac Event (Retrospective European Multicenter Study)
Agostini et al. Jacobson. Eur J Nucl Med Mol Imaging. 2008;35: 535-546.
290 CHF pts. In 6 European Centers during 10 yr. period.
MCE: Cardiac death, transplant, potentially fatal arrhythmia (including ICD discharge)
18 studies, 1755 patients
Cardiac death
Cardiac
events (cardiac death, MI, transplant, HF hospitalization)
MBG Washout MIBG and Mortality
MIBG diminuído esteve associado a 10X maior mortalidade
MIBG, BNP and Adverse events
MIBG
UFF & Pro-Cardiaco
B1-adrenoreceptor polymorphisms in heart
failure patients and its relationship to
cardiac I123-MIBG and carvedilol
treatment response
ET. Mesquita1, SM. Miranda1, S D. Moscavitch1, SB. Pereira1, RA. Freitas1, JC. De
Azevedo2, LR. Messias1, RC. Rodrigues1, GS. Ribeiro1, CT. Mesquita2
-20%
-10%
0%
10%
20%
30%
Ser49Ser Ser49Gly ou Gly49Gly
Washout 49Gly xSer49Ser.
Interleukin 1β levels correlate with MIBG
and exercise parameters, in heart failure? Messias L, Miranda S, Mesquita CT, et al.
Arq Bras Cardiol, in press
MIBG en Arritmias
What Causes Sudden Cardiac Death in CHF?
Of CHF deaths: 50% are sudden and unexpected (6-9x general population)
Presumption: mostly VT/VF, but increasing % from bradyarrhythmias and EMD
Medical therapy for CHF may be lessening disposition to VT/VF
PATHOPHYSIOLOGY
Myocardial ischemia
Action potential prolongation/dispersion of repolarization
Disruption of K, Na, Ca channels
Altered conduction
Inexcitable barriers and tissue discontinuities
Genetic predisposition
Altered neurohormonal signaling
RAAS activation
Autonomic abnormalities : Global disruption, regional heterogeneities of sympathetic
innervation
Tomaselli, Zipes. Circ Res 2004; 95: 754-63.
RELATIONSHIP OF MIBG AND HRV
VARIABLES TO ICD DISCHARGES
0
100
200
300
400
500
600
700
800
900
1 1,1 1,2 1,3 1,4 1,5 1,6 1,7 1,8 1,9 2 2,1
EARLY HMR
(lf)
ICD Discharge NO ICD Discharge
Group II
Group I
Group IV
Group III
(lf) = 443
HMR = 1.54
Arora R et al Travin MI . J Nucl Cardiol 2003;10:121-31.
*
* p = 0.03 compared with Group IV
54 patients with ICD
Predicting the Need for ICD with MIBG, BNP and LVEF
Nagahara D, Nakata et al. . J Nucl Med 2008; 49: 225-
233.
Jacobson AF. Presented at American College of Cardiology 58th Annual
Scientific Session, March 29-31, 2009, Orlando, Florida.
Senior R et al., Circulation 2009; 120. Presented at AHA
2009
25% of pts.
123I-MIBG H/M Improves Risk Stratification Beyond the Seattle Heart Failure Model
Ketchum E, Jacobson A, Caldwell J, Senior R, Cerqueira M, Thomas G, Agostini D, Narula J, Levy W. J Nucl Cardiol 2012, in press
961 ADMIRE-HF patients
Tomographic MIBG Assessing Regional Abnormalities
ICD PATIENT: NO SHOCK
LATE MIBG AND REST SESTAMIBI SPECT IMAGES
ICD PATIENT: SHOCK
LATE MIBG AND REST SESTAMIBI SPECT IMAGES
MIBG Image Findings in Relation to
Occurrence of ICD Discharges
0
5
10
15
20
25
30
35
40
45
123I-MIBG 123I- MIBG/99mTc-Sestamibi
Defect Score Mismatch Score
ICD + ICD - CONTROLS
0
0,5
1
1,5
2
2,5
3
HMR
n = 10 7 2 10 7 2 10 7 2
1.45 1.68 1.92 41.3
8.6
18.0
7.5 3.4 0
p < 0.05
p < 0.05
p < 0.05
Arora R et al Travin MI . J Nucl Cardiol 2003;10:121-31.
Sympathetic Denervation Assessed with 123I-MIBG Imaging
Predicts Ventricular Arrhythmias in ICD Patients
Boogers et al. Bax. J Am Coll Cardiol 2010; 55; 2769-77.
116 patients with CHF referred for ICD therapy
Difference in appropriate ICD therapy: Late MIBG SSS > 26 vs. SSS < 26
What SPECT Parameters Should be Measured?
Summed score
Would we expect parameters useful for perfusion imaging to also work for
autonomic imaging?
Caution! Different from perfusion imaging in that uptake of the entire
myocardium is often abnormal.
Heterogeneity measure of some type
Maximum – minimum
Spread function
MIBG/Perfusion Mismatch
Severity
Area
Distribution
123I-mIBG PARAMETERS:
High HMR
Low W.O.
High negative predictive value for
lethal arrhythmias and SCD
Thanks
Dr. Mark Travin
http://www.huap.uff.br/medicinanuclear/