Mulher de 79 anos admitida no PS com 3hrs de dor torácica ... · • Mulher de 79 anos admitida no...

• 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.