CASO CLINICO
• Mulher de 79 anos admitida no PS com
3hrs de dor torácica e dispnéia.
• FC 66, PA: 130/80, Sat O2:90%
ECG no PS
Pergunta
Qual dos tratamentos abaixo não deve
ser realizado?
a) AAS
b) Clopidogrel
c) Anti-inflamatórios não hormonais
d) Nitrato
e) Oxigenio
Resposta
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)
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
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?
a) Cineangiocoronariografia visando
angioplastia primária
b) Trombólise com SK
c) Trombólise com tPA
d) Cirurgia de revascularização miocárdica
Coronária Esquerda OK
Coronária Direita OK
Hipocontratilidade segmentar significativa
Marcadores de necrose miocárdica
CK: (U/L)
Troponina I (ng/ml)
CK-MB: (ng/ml)
378 (normal <170)
3,02 (normal <0,4)
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.
Pergunta
Qual o diagnóstico?
a) Miocardite
b) Espasmo coronário
c) Choque anafilático
d) TEP
e) Nenhuma das anteriores
Resposta
Qual o diagnóstico?
a) Miocardite
b) Espasmo coronário
c) Choque anafilático
d) TEP
e) Nenhuma das anteriores
Villaroel A, Vitola J, Stier A, Dippe T, Cunha C. Expert Rev. Cardiovasc. Ther., 7 (7) 2009
New Imaging Targets: Autonomic Nervous System – MIBG
The Impact on Heart Failure and Sudden Cardiac Death Risk Stratification
João V. Vitola, MD, PhD
Cardiologist and Nuclear Medicine Physician
Quanta Diagnostico Nuclear
Curitiba - Brazil
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
• MIBG (Meta-Iodo-Benzyl-Guanidine)
– a physiologic analog of the sympathetic nervous
system neurotransmitter norepinephrine (NE).
OH
I
NH
OH
CH2NH-C-NH2
CHCH2NH2
OH
NOREPINEPHRINE
MIBG
MIBG (Meta-Iodo-Benzyl-Guanidine)
• 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
NERVE
TERMINAL
NE
VMAT
α2c
NET1
SYNAPTIC
CLEFT
NE
α + β receptors
BLOOD VESSEL
NE
MIBG
COMT
NMN
EFFECTOR
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 presynaptic 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
H/M ratio: 2.2
NYHA Class II
1.7
NYHA Class IV
1.1
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.
MIBG IMAGING
Parameters Assessed
• Global cardiac uptake of tracer (planar, delayed images)
– Heart/mediastinal ratio.
mean).
2.2 ± 0.3 (<1.6 is 2 SD below normal
• 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)
Mean H/M: 1.44
Median H/M: 1.42
Proportion (%)
H/M Ratio
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-m IBG (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
964 HF subjects were evaluable for efficacy
Variable
Data
Range
62.4
20-90
Gender (M/F) (%)
80/20
-
Race (W/B/O) (%)
75/14/1
1
-
NYHA II/III (%)
83/17
-
HF Etiology (I/NI*)
(%)
66/34
-
Mean LVEF (%)
27
5-35
Median Follow-up
(mo)
17
0.1-27
12.8
-
Mean Age (yr)
2-year mortality rate
(%)
*I=Ischemic; NI=Non-ischemic
Adverse Cardiac Events
238 subjects (25%) had an adverse cardiac event.
Subjects n (row %) with Event of:
HF
Arrhythmic Cardiac
Total
Progression
Event
Death
First Event
163 (68)
51 (21)
24 (10)
238
52 subjects had a second event of a different category
following a HF progression or arrhythmic event.
Subjects n (row %) with Event of:
HF
Arrhythmic
Progression
Event
All Events
176 (60)
64 (22)
Cardiac
Death
Total
53* (18)
294
*23 SCD, 24 progressive HF, 6 other
Cardiac Death Event
H/M≥1.60: 2-year
event-free survival 98%
Event-free
Survival
Probability
H/M<1.60: 2-year
event-free survival 89%*
Time (days)
*p=0.002 vs H/M ≥1.60
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
4 hour H/M ratio
LVEF
BNP
Plasma NE
NYHA Class
Systolic BP
Hazard Confidence
ratio
Limits
0.385
0.977
1.000
1.000
1.621
0.991
0.177;
0.964;
1.000;
1.000;
1.159;
0.983;
0.839
0.989
1.001
1.001
2.266
0.998
p
0.016
0.0003
0.007
0.013
0.005
0.016
All-cause Mortality vs LVEF & H/M
MIBG a better predictor compared to LVEF
LVEF≥30%, H/M≥1.60*
LVEF<30%, H/M ≥1.60**
Survival
Probability
LVEF≥30%, H/M<1.60
LVEF<30%, H/M<1.60
Time (days)
*p=0.006 vs LVEF≥30%,
H/M<1.60
**p=0.023 vs LVEF<30%,
H/M<1.60
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).
1
H/M=0.96
Died at 8 mo
HF Progression
2
H/M=1.38
Died at 8 mo, SCD
(No ICD)
3
H/M=1.67
No event
Based upon the results of ADMIRE-HF, 2-year cardiac mortality risk
for patient 1 is 10 times that of patient 3.
Primary Efficacy Analysis
H/M≥1.60: 2-year
event-free survival 85%
Event-free
Survival
Probability
H/M<1.60: 2-year
event-free survival 63%*
*p<0.0001 vs H/M ≥1.60
Time (days)
n: Low H/M: 760
High H/M: 201
732
195
658
179
562
157
462
136
356
109
265
79
149
52
Arrhythmic Event
H/M≥1.60: 2-year
event-free survival 96%
Event-free
Survival
Probability
H/M<1.60: 2-year
event-free survival 85%*
Time (days)
*p=0.002 vs H/M ≥1.60
Relationship of Type of Cardiac Event and H/M Ratio
25
Proportion 20
of Subjects
15
with Events
(%)
10
H/M Ratio
<1.30
1.30-1.59
≥1.60
5
0
HF
Arrhythmic
Progression
Event
2-Year HF and Arrhythmic Event Probability vs H/M Ratio
30
25
2-Year Event
Probability
(%)
H/M Ratio
20
<1.30
1.30-1.59
≥1.60
15
10
5
0
HF Prog
Arr
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
30
25
2-Year
Mortality
Rate (%)
20
Cardiac Death
15
All Cause
Mortality
10
5
0
<1.20
1.201.39
1.401.59
≥1.60
Late H/M Ratio (4 hrs)
Relationship of HF Deaths and Arrhythmic Events to H/M
Ratio in Subjects with ICDs (n=381)
Arrhythmic events
HF Deaths
Proportion
of
Subjects
with
Events (%)
6
5
4
3
2
1
0
20
15
10
Non-SCD
SCD
5
<1.30 1.30- ≥1.60
1.59
H/M Ratio
0
<1.30
1.301.59
≥1.60
H/M Ratio
Relationship of HF Deaths and Arrhythmic Events to H/M
Ratio in Subjects without ICDs (n=580)
Arrhythmic events
HF Deaths
Proportion
of
Subjects
with
Events (%)
6
5
4
3
2
1
0
<1.30 1.30- ≥1.60
1.59
H/M Ratio
6
5
4
3
2
1
0
Non-SCD
SCD
<1.30
1.301.59
≥1.60
H/M Ratio
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.