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• Mulher de 79 anos admitida no PS com 3hrs de dor torácica e dispnéia.
• FC 66, PA: 130/80, Sat O2:90%
CASO CLINICO
ECG no PS
a) AAS b) Clopidogrel c) Anti-inflamatórios não hormonais d) Nitrato e) Oxigenio
Pergunta Qual dos tratamentos abaixo não deve
ser realizado?
a) AAS (Classe I) b) Clopidogrel (Classe I) c) Anti-inflamatórios não hormonais (Classe
III) d) Nitrato (Classe I) e) Oxigenio (Classe I)
Resposta Qual dos tratamentos abaixo não deve
ser realizado?
Baseado em: Piegas et al; IV Diretriz da Sociedade Brasileira de Cardiologia sobre Tratamento do Infarto Agudo do Miocárdio com Supradesnível do Segmento ST. Arq Bras Cardiol 2009; 93(6 Supl. 2): e179-e264
a) Cineangiocoronariografia visando angioplastia primária
b) Trombólise com SK c) Trombólise com tPA d) Cirurgia de revascularização miocárdica
Pergunta Qual a melhor estratégia visando a
reperfusão em serviços com hemodinâmica disponível?
a) Cineangiocoronariografia visando angioplastia primária
b) Trombólise com SK c) Trombólise com tPA d) Cirurgia de revascularização miocárdica
Resposta Qual a melhor estratégia visando a
reperfusão em serviços com hemodinâmica disponível?
Coronária Esquerda OK
Coronária Direita OK
Hipocontratilidade segmentar significativa
Marcadores de necrose miocárdica CK: (U/L) 378 (normal <170) Troponina I (ng/ml) 3,02 (normal <0,4) CK-MB: (ng/ml) 19,7 (normal< 3,4)
• Resumo da apresentação clínica: dor torácica prolongada, dispnéia, supra de ST, marcadores de necrose miocárdica elevados, coronárias “normais”, disfunção segmentar de VE importante.
• No seguimento – Choque cardiogênico – Edema agudo de Pulmão – Admitida na UCO, entubação, inotrópicos EV.
a) Miocardite b) Espasmo coronário c) Choque anafilático d) TEP e) Nenhuma das anteriores
Pergunta Qual o diagnóstico?
a) Miocardite b) Espasmo coronário c) Choque anafilático d) TEP e) Nenhuma das anteriores
Resposta Qual o diagnóstico?
Villaroel A, Vitola J, Stier A, Dippe T, Cunha C. Expert Rev. Cardiovasc. Ther., 7 (7) 2009
DISCLOSURES
Honorarium – Research / Advisor, Expert Services and Conferences in Nuclear Cardiology
BMS, CVT, Astellas, Lantheus, PPGx, IAEA
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, MD, PhD
Cardiologist and Nuclear Medicine Physician Quanta Diagnostico Nuclear
Curitiba - Brazil
New Imaging Targets: Autonomic Nervous System – MIBG
The Impact on Heart Failure and Sudden Cardiac Death Risk Stratification
• MIBG (Meta-Iodo-Benzyl-Guanidine) – a physiologic analog of the sympathetic nervous
system neurotransmitter norepinephrine (NE).
I
CH2NH-C-NH2
NH
MIBG
CHCH2NH2
OH
OH
OH
NOREPINEPHRINE
• Semelhança da estrutura molecular com a da
noradrenalina permite que ambos utilizem o mesmo mecanismo de captação e armazenamento na fenda simpática terminal.
• Quando ligado ao Iodo 123 possibilita a visualização do SNS pela cintilografia
MIBG (Meta-Iodo-Benzyl-Guanidine)
NE NE
NE
NMN
COMT α + β receptors
α2c NET1
NERVE TERMINAL
EFFECTOR
SYNAPTIC CLEFT
BLO
OD
VES
SEL VMAT
MIBG MIBG enters the synaptic cleft and is taken up into the neuron by NET.
With heart disease (CHF), there may be reduction in the number of pre-synaptic neurons and the function of the NET, resulting in decreased uptake of MIBG.
Hipocontratilidade segmentar significativa
99Tc MIBI at rest
123I-MIBG
Prognostic Significance of 123I-MIBG Myocardial Scintigraphy in Heart Failure Patients: Results from the Prospective
Multicenter International ADMIRE-HF Trial
*ADMIRE-HF: AdreView Myocardial Imaging for Risk Evaluation in Heart Failure
Jacobson A et al. ACC, 2009
123I-MIBG Cardiac Imaging
• Studied in Japan and Europe for 2 decades as a marker of prognosis in heart failure
• - The lower the uptake, the poorer the outcome
• Limitations of prior studies 1. Single-center experiences
• 2. No standardization of uptake analysis methodology
• 3. Diagnostic criteria and endpoints were not always prospectively established
[123I]mIBG Planar Imaging for Cardiac Assessment
Normal innervation NYHA Class II NYHA Class IV
Quantitation of cardiac uptake of [123I]mIBG expressed in terms of the ratio of counts/pixel between regions of interest (ROIs) drawn around the heart (H) and in the upper mediastinum (M), the H/M ratio.
H/M ratio: 2.2 1.7 1.1
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.
Distribution of H/M ratios in HF Subjects (n=961)
Proportion (%)
H/M Ratio
Mean H/M: 1.44 Median H/M: 1.42
Primary Objective of ADMIRE-HF To demonstrate the prognostic usefulness of assessment of myocardial sympathetic innervation, as determined by the heart to mediastinum (H/M) ratio on planar 123I-mIBG imaging as either normal (>1.6) or abnormal (<1.6), for identifying HF subjects at higher risk of experiencing an adverse cardiac event.
Secondary Objective of ADMIRE-HF To determine the utility of assessment of myocardial sympathetic innervation for quantifying risk for adverse cardiac events due to heart failure and ventricular arrhythmias.
– Primary eligibility criteria • NYHA II/III HF (ischemic or non-ischemic) • LVEF≤35% • Guidelines-based management including ACE inhibitors
and beta blockers.
– 123I-mIBG (AdreViewTM) imaging procedures • Early (15 min) and late (4 hr) planar and SPECT • Interpretation by 3 blinded readers at an independent
core lab
Determination of outcome events • Follow-up data collected every 6 weeks for a maximum of
2 years • Composite of the following 3 categories of events used
for primary analyses – HF Progression: Progression of HF stage (NYHA II to III or
IV, III to IV). – Arrhythmic Event: Episode of sustained ventricular
tachyarrhythmia (VT); appropriate ICD discharge; or aborted cardiac arrest.
– Terminal Cardiac Event: Cardiac death.
Subject Demographics and Clinical Characteristics
Variable Data Range Mean Age (yr) 62.4 20-90
Gender (M/F) (%) 80/20 -
Race (W/B/O) (%) 75/14/11
-
NYHA II/III (%) 83/17 -
HF Etiology (I/NI*) (%)
66/34 -
Mean LVEF (%) 27 5-35
Median Follow-up (mo)
17 0.1-27
2-year mortality rate (%)
12.8 -
964 HF subjects were evaluable for efficacy
*I=Ischemic; NI=Non-ischemic
Adverse Cardiac Events
Subjects n (row %) with Event of: HF
Progression Arrhythmic
Event Cardiac Death
Total
First Event 163 (68) 51 (21) 24 (10) 238
238 subjects (25%) had an adverse cardiac event.
Subjects n (row %) with Event of: HF
Progression Arrhythmic
Event Cardiac Death
Total
All Events 176 (60) 64 (22) 53* (18) 294
52 subjects had a second event of a different category following a HF progression or arrhythmic event.
*23 SCD, 24 progressive HF, 6 other
Time (days)
Event-free Survival Probability
H/M<1.60: 2-year event-free survival 89%*
Cardiac Death Event
*p=0.002 vs H/M ≥1.60
H/M≥1.60: 2-year event-free survival 98%
Low Cardiac MIBG uptake = Marker of High Mortality Rate
Multivariable Analysis Cox proportional hazard analysis identified 6 variables as independent predictors of the composite endpoint.
Variable Hazard ratio
Confidence Limits
p
4 hour H/M ratio 0.385 0.177; 0.839 0.016 LVEF 0.977 0.964; 0.989 0.0003 BNP 1.000 1.000; 1.001 0.007 Plasma NE 1.000 1.000; 1.001 0.013 NYHA Class 1.621 1.159; 2.266 0.005 Systolic BP 0.991 0.983; 0.998 0.016
All-cause Mortality vs LVEF & H/M MIBG a better predictor compared to LVEF
Survival Probability
Time (days)
LVEF<30%, H/M<1.60
LVEF≥30%, H/M≥1.60*
*p=0.006 vs LVEF≥30%, H/M<1.60 **p=0.023 vs LVEF<30%, H/M<1.60
LVEF<30%, H/M ≥1.60**
LVEF≥30%, H/M<1.60
H/M=0.96 Died at 8 mo HF Progression
H/M=1.38
Died at 8 mo, SCD (No ICD)
H/M=1.67
No event
1 2 3
Three Patients with NYHA Class II HF and LVEF between 20 and 25%. Patient 1 has highly elevated BNP (>1000). BNP in patients 2 and 3 is normal (<100).
Based upon the results of ADMIRE-HF, 2-year cardiac mortality risk for patient 1 is 10 times that of patient 3.
Time (days)
Event-free Survival Probability
H/M≥1.60: 2-year event-free survival 85%
H/M<1.60: 2-year event-free survival 63%*
Primary Efficacy Analysis
*p<0.0001 vs H/M ≥1.60
n: Low H/M: 760 732 658 562 462 356 265 149 High H/M: 201 195 179 157 136 109 79 52
Time (days)
Event-free Survival Probability
H/M≥1.60: 2-year event-free survival 96%
H/M<1.60: 2-year event-free survival 85%*
Arrhythmic Event
*p=0.002 vs H/M ≥1.60
Relationship of Type of Cardiac Event and H/M Ratio
0
5
10
15
20
25
HFProgression
ArrhythmicEvent
<1.301.30-1.59≥1.60
H/M Ratio Proportion of Subjects with Events
(%)
2-Year HF and Arrhythmic Event Probability vs H/M Ratio
05
1015202530
HF Prog Arr
<1.301.30-1.59≥1.60
H/M Ratio 2-Year Event Probability
(%)
Differences between H/M≥1.60 and other groups are all significant (p<0.05). Differences between H/M<1.30 and 1.30-1.59 are both p>0.05.
2 Year Mortality vs. H/M Ratio
0
5
10
15
20
25
30
<1.20 1.20-1.39
1.40-1.59
≥1.60
Cardiac Death
All CauseMortality
2-Year Mortality Rate (%)
Late H/M Ratio (4 hrs)
Relationship of HF Deaths and Arrhythmic Events to H/M Ratio in Subjects with ICDs (n=381)
H/M Ratio
Proportion of
Subjects with
Events (%) 0
5
10
15
20
<1.30 1.30-1.59
≥1.60
Non-SCDSCD
H/M Ratio
Arrhythmic events HF Deaths
0123456
<1.30 1.30-1.59
≥1.60
Relationship of HF Deaths and Arrhythmic Events to H/M Ratio in Subjects without ICDs (n=580)
H/M Ratio
Proportion of
Subjects with
Events (%) 0123456
<1.30 1.30-1.59
≥1.60
Non-SCDSCD
H/M Ratio
Arrhythmic events HF Deaths
0123456
<1.30 1.30-1.59
≥1.60
Conclusions
• 1. 123I-MIBG cardiac imaging has independent prognostic capability that is complementary to other commonly used markers such as LVEF and BNP.
• 2. HF patients can be divided into risk groups based upon planar H/M ratios. A patient with H/M ≥ 1.60 has a low risk for cardiac mortality over two years.
• 3. Risk for HF mortality and arrhythmic events appears to show different tendencies in the H/M range 1.0-1.60.
