Myocardial Viability and Survival
in Ischemic Left Ventricular Dysfunction
Robert O. Bonow, MD
On behalf of the STICH Trial Investigators
Background
• LV dysfunction in patients with CAD is not
always an irreversible process, as LV function
may improve substantially after CABG
• Assessment of myocardial viability is often
used to predict improvement in LV function after
CABG and thus select patients for CABG
• Numerous studies have suggested that
identification of viable myocardium also predicts
improved survival after CABG
STICH Viability Hypothesis
In this prospective substudy, we tested the
hypothesis that assessment of myocardial
viability identifies patients with CAD and LV
dysfunction who have the greatest survival
benefit with CABG compared to aggressive
medical therapy
STICH Viability Hypothesis
• All randomized patients were eligible for
viability testing with SPECT myocardial
perfusion imaging or dobutamine echo.
• Viability testing was optional at enrolling
sites and was not a prerequisite for
enrollment.
Questo è un evidente bias di selezione, e non è
stato controllato (forse non è controllabile in un trial
di questo genere: è un sottostudio)
STICH Viability Hypothesis!!!!
SPECT protocols:
• Thallium-201 stress-redistribution-reinjection
• Thallium-201 rest-redistribution
• Nitrate-enhanced Tc-99m perfusion imaging
Dobutamine echo protocols:
• Staged increase in dobutamine starting at
5 μg/kg/min
Quanti hanno fatto il tallio e quanti il tecnezio? Dato
mancante. Il tallio stava uscendo dal mercato,
arguiamo: pochi pz con tallio? La perfusione con
tecneziati sottostima gravemente la vitalità,
SPECIALMENTE L’IBERNAZIONE
Patients randomized in STICH
Revascularization Hypothesis
1212
SPECT
n=471
Dobutamine echo
n=280
321 150 130
611
Patients with
usable myocardial
viability test
601
114
487
Viable
Nonviable
Patients with no
usable myocardial
viability test
Baseline Characteristics
Patients With and Without Myocardial Viability
Variable
Viable
(n=487)
Non-Viable
(n=114)
P value
Age
61 ± 10
61 ± 9
NS
Multivessel CAD
73%
73%
NS
Proximal LAD stenosis
64%
70%
NS
Risk score *
12.4 ± 8.7
12.9 ± 9.3
NS
Previous MI
76.6%
94.7%
<0.001
LV ejection fraction (percent)
28 ± 8
23 ± 9
<0.001
LV end-diastolic volume index (ml/m2)
117 ± 37
147 ± 53
<0.001
LV end-systolic volume index (ml/m2)
86 ± 33
116 ± 50
<0.001
* Significant covariates in risk model: Age, renal function, heart failure,
ejection fraction, CAD index, mitral regurgitation, stroke
E gli altri 611??????
Myocardial Viability and Mortality
Without Viability
1.0
Mortality Rate
0.8
With Viability
MED (33 deaths)
MED (95 deaths)
CABG (25 deaths)
CABG (83 deaths)
56%
0.6
35%
0.4
42%
31%
0.2
0.0
0
1
2
3
4
5
Years from Randomization
MED
60
51
44
39
29
CABG
54
48
41
41
34
6
0
1
2
3
4
5
Years from Randomization
6
14
4
243
219
206
179
146
94
51
22
12
244
213
203
192
148
94
51
Contraddice tutti gli altri studi, la metanalisi, e non ha
senso fisiopatologico. Come è potuto accadere?
“Dov’è l’errore?”
STICH Viability Hypothesis
Limitations:
• Lack of viability data in all patients; patients
represent a subpopulation of STICH
• Analysis limited to SPECT and dobutamine
echo, not PET or cardiac MRI
Ah, ecco perché!
VARIABILITÀ INTERLABORATORIO DELLA
VALUTAZIONE DELLA CINETICA
REGIONALE DEL VENTRICOLO SINISTRO
CON ECO 2D
Confronto Esperti vs. Cardiologi liguri
Concordanza fra 6 Esperti
51+11%
Concordanza fra 44 Cardiologi liguri 41+14%
Luigi Badano, 1994
Eco-dobutamina per la vitalità in un
grande trial? Senza lettura centrale?
Eppure era noto che le ripetibilità
dell'esecuzione, della lettura e
dell'interpretazione erano scarse e
troppo operatore-dipendente per
l'ecocardiografia da stress
farmacologico…
ECO-dobutamina per la vitalità: studi clinici
Storia della Medicina: a seguito dell'utilizzo di un test
provocativo farmacologico (artefattuale in quanto non
fisiologico), nel decorso clinico, a scopo di ricerca, la
metodica in studio (ecocardiografia) è stata anche la
metodica di riferimento per il giudizio dei risultati ottenuti
(miglioramento di cinesi), e nemmeno in condizioni di
cecità (in a “publish or perish world”)!! E’ una metodica
valida per uno studio multicentrico senza lettura
centralizzata?
Area di commento libero
Ma che STICH
e
Survey of medical imaging modalities
Multimodality imaging devices such as SPECT/CT, PET/CT and PET/MRI
encompass the whole spectrum of preclinical and clinical imaging
Schober O et al. Eur J Nucl Med Mol Imaging 2009
18-FDG
VANTAGGI:
- migliore tecnologia PET vs SPET (risoluzione,
attenuazione, effetto volume parziale, contrast
recovery, migliori aspetti quantitativi)
- scarsa dipendenza dal flusso (“tallone
d’Achille”della SPET, specie dei tecneziati)
Gianni Bisi, 2004
Cardiac Tomography After Nitrate Administration in Patients With
Ischemic LV Dysfunction: Relation to Metabolic Imaging by PET
Patient 1
Patient 2
He Wei et al. J Nucl Cardiol 2003
Survival by Viability and Treatment
93 Patients with Ischemic Cardiomyopathy and severely depressed
left ventricular function
Survival Probability
With PET
Mismatch
Without PET
Mismatch
1.0
1.0
CABG
0.8
0.6
p = 0.007
Medical
0.4
0.8
CABG
0.6
Medical
0.4
0.2
0.2
NS
0.0
0.0
0
12
24
36
48
Time (months)
Di Carli et al, J Thor Cardiovasc Surg 1998; 116: 997
60
0
12
24
36
48
Time (months)
60
Nuclear Imaging Predicts
Long-Term Outcome After CABG
100
More Viability
Less Viability
% Event-free
90
70
p=0.025
50
30
0
12
24
36
Time (Months)
From Pagley et al. J Am Coll Cardiol 1996;27:299A.
48
60
Adjusted survival curves for PET and
standard arms in Ottawa-FIVE substudy
Abraham1 A, J Nucl Med 2010; 51:567–574
FDG IMAGING IN LV ANEURYSMS
70 pts with LV aneurysm
6.8 yrs FU
Surgery for viability improved
EF and survival (p .0001)
Medical therapy with viability
had worst outcome (p .0001)
Zhang X et al J Nucl Med 2008; 49:1288–1298
STICH Viability Hypothesis
Implications:
In patients with CAD and LV dysfunction,
assessment of myocardial viability does not
identify patients who will have the greatest
survival benefit from adding CABG to
aggressive medical therapy
Questo, proprio, no. Tra “viability” e “does”
sarebbe stato il caso di aggiungere “, in the way
STICH Investigators did,” ma era l’ultima
diapositiva, sembrava pedante…
Myocardial Viability and Impact of
Revascularization
Meta-analysis of 24 studies in 3,088 patients
Death rate (%/yr)
30
25
-79.6%
+23%
p < 0.0001
20
16
p = 0.23
Revasc
Medical
15
7,7
10
5
6,2
3,2
0
Viable
Nonviable
Allman et al. J Am Coll Cardiol 2002
“Dopo lo STICH, la vitalità non è più un criterio per l’indica
zione a CABG”
“Dove
stiamo
andando
?”
Ma che STICH
e
Scarica

Myocardial Viability and Survival in Ischemic Left Ventricular