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Ruolo della rivascolarizzazione
miocardica nello scompenso cardiaco
Francesco Amico
U.O. Dip. Emodinamica - Caltanissetta
Heart Failure Prevalence Will Double in 30 Years
• Aging population
• Coronary disease
management
HF Prevalence in Western Europe (Millions)
5.3
10.6
0
2
4
6
8
10
12
2000 2010 2020 2030
Source: New Medicine Reports 1997 ; 1999 Heart and Stroke Statistical Update, AHA
Eziologia dello scompenso cardiaco
nello studio di Framingham Ho KK et al, J Am Coll Cardiol 1993; 22(Supplement A):6A-13A
No HTN or CHD
Hypertensionalone
CHD+HTN
CHD alone
MEN WOMEN
CHD = coronary heart disease
HTN = hypertension
40%
19% 11%
30% 40%
7% 15%
37%
Rivascolarizzazione… HF
STUDI
Ruolo della vitalità
• Osservazionali
Funzione ventricolare sn
Qualità della vita
Sopravvivenza
• Randomizzati
Sopravvivenza
3/31/2015
1
Role of Revascularization in
Patients with Severe LV
Dysfunction
Joseph F. Sabik, III, MD
Chairman and Professor of Surgery
Department of Thoracic and Cardiovascular Surgery
Sheik Hamdam Bin Rashid Al Maktoum Distinguished Chair
Cleveland Clinic Lerner College of Medicine
CASS Registry - LVEF <0.35 Medical vsSurgical Survival
Alderman et al Circ 1983
100
80
60
40
20
0
% S
urv
iva
l
0 1 2 3 4 5 76
Months of Follow-up
Medical
Surgical
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2
Medical
Surgical
CASS Registry - LVEF < 0.35% Cardiac Event Free Survival - Angina
100
80
60
40
20
00 1 2 3 4 7
Years
%
65
P=.0006
Medical
100
80
60
40
20
00 1 2 3 4 7
Years
%
65
P=.6687
CASS Registry - LVEF < 0.35% Event Free Survival - Heart Failure
Surgical
3/31/2015
2
Medical
Surgical
CASS Registry - LVEF < 0.35% Cardiac Event Free Survival - Angina
100
80
60
40
20
00 1 2 3 4 7
Years
%
65
P=.0006
Medical
100
80
60
40
20
00 1 2 3 4 7
Years
%
65
P=.6687
CASS Registry - LVEF < 0.35% Event Free Survival - Heart Failure
Surgical
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3
LV dysfunction is a potentially
reversible phenomenon with
revascularization
Viability
Myocardial stunning
Myocardial hibernation
StudiesRole of Viability
• Observational
• LV Function
• Quality of Life
• Survival
• Randomized
• Survival
progressively increasing angina despite medical therapy and
angina 2 weeks after MI, (43) that is, those in Braunwald
classes B and C; II and III (44), and in most patients with
severe, chronic stable angina, because revascularization is
often undertaken in these patients for relief of symptoms.
However, one must recognize that 1) the severity of angina
maynot relate to theextent of myocardium at risk, extent and
severity of CAD and LV function (45); 2) in patients with
angina (if one excludes unstable angina), the extent of CAD
and LV function and the extent and severity of ischemia are
predictors of outcome but angina is not (2,46,47); and 3)
documentation of theamount of hibernatingmyocardiummay
allowbetter assessment of therisksandbenefitsof revascular-
ization (see above). Post-MI patients pose a more difficult
problem because of the complexity and variety of clinical
situationsthat maybepresent. These include theclinical state
of thepatient, location of theMI, extent and severityof CAD,
extent and severity of LV dysfunction and the feasibility of
revascularizing all dysfunctional myocardial segments; thus,
the need to revascularize some or all dysfunctional LV seg-
mentsmay require evaluation by testing for hibernating myo-
cardium. Anomalous left coronary artery from pulmonary
artery (ALCAPA) isacongenital disorder that often presents
with LV dysfunction or heart failure with or without mitral
regurgitation, and theclinical findingsmaybesimilar to those
for idiopathicdilated cardiomyopathy. ThesevereLV dysfunc-
tion and dilation improvesor normalizesafter surgical correc-
tion (48–54) (Fig. 2). Pathologic studies of transmural myo-
cardial biopsyspecimenshaveshown changesthat arethoseof
“structural adaptation to chronic ischemia” (53) and are
similar to thosedescribed inhibernatingmyocardium. Patients
with ALCAPA should be diagnosed early and should have
early reimplantation of the left coronary artery into theaorta.
Those with severe LV dysfunction may need testing for
hibernating myocardium. In all the above clinical syndromes,
there isaneed for clinical judgment. It must also be borne in
mind that in all theabovesubgroupsof patients, assessment of
hibernating myocardium may allow better assessment of the
risks and benefits of revascularization; however, additional
studiesare needed that document thispremise.
Revascularization for hibernating myocardium. Function
in hibernatingmyocardiumimprovesor normalizeswith revas-
cularization, but the effects of optimal medical therapy have
not beenevaluated. Factorstobeconsidered inrecommending
revascularization areshown in Table 5. Important factorsthat
are likely to determine the expected improvement in LV
function and hence patient outcome are an estimate of the
extent of irreversibly damaged myocardium and the extent of
hibernating myocardium (55,56). Haas et al. (18) used three
criteria to recommend revascularization for patients in Group
B,oneof whichwasviablemyocardium(seeearlier). Theother
two were extent of necrosis and viable tissue. Although these
were determined subjectively, it is, nevertheless, an important
direction to pursue in determining whether patients should
undergo revascularization. Additional studiesare needed.
Some additional studies that are needed. The need for
large, randomized studiestoconfirm thefindingof Haaset al.
(18), as suggested by the authors, may be premature at this
time (57) because of the limitations of their study. The
predictive accuracy of tests for diagnosis of hibernating myo-
cardium may be inaccurate in 15% to 30% of patients; we do
not know which test or combinations of tests is best for
diagnosisof hibernatingmyocardiumineachclinical syndrome
Figure 2. Preoperative (Pre-op) and postoperative LV end-diastolicvolume (EDV) index (left) and LV ejection fraction (EF) (right) infivepatients2 to 8.5 yearsold who underwent surgical correction forALCAPA. d days after operation; mos months after operation;CM data from patients with IDCM at the author’s institution.Reproduced, with permission, from Rein et al. (49).
Table 5. Some Factors to Be Considered in Clinical DecisionMaking When Considering Revascularization forHibernating Myocardium
Suitability of coronary arteries for revascularization
Severity of LV dysfunction
Symptoms, especially angina
Extent of irreversibly damaged myocardium
Extent of HM
Risks of revascularization
Estimate of LV functional recovery after revascularization
HM hibernating myocardium; LV left ventricular.
1704 RAHIMTOOLA JACC Vol. 30, No. 7EDITORIAL COMMENT December 1997:1701–6
3/31/2015
13
1.0
0.8
0.6
0.4
0.2
00 1 2 3 4 5 6
Mort
alit
y R
ate
Years Following Randomization
Med
MortalityAs Treated Analysis (During Year 1)
CABG
HR 0.70 95% CI(0.58, 0.84) P<0.001
Velazquez EJ et al.: N Engl J Med 2011;364:1607-16. Supplement
3/31/2015
14
STICH TrialMyocardial Viability
• 1212 patients
• 601 Viability Testing
•298 Medical therapy plus CABG
•303 Medical therapy
1.0
0.8
0.6
0.4
0.2
00 1 2 3 4 5 6
Pro
ba
bili
ty o
f D
eath
Years since Randomization
With Viability
Bonow et al.: N ENGL J MED 364;17, April 28, 2011
HR 0.64 (95% CI, 0.48-0.86)
P=0.003
Without Viability
MortalityMyocardial Viability
Mortalità a 30 gg CABG 4% - TM 1% Solo 50% dei pazienti sottoposto a test di vitalità Esclusione dei pazienti con malattia del Tronco Comune Inclusione di pazienti con cardiomiopatia non ischemica
ITT
Coronary Revascularization in Ischemic Heart Failure Patients: A Rapid Review. January 2013; pp. 1–28.
Coronary Revascularization in
Ischemic Heart Failure Patients:
A Rapid Review
G Pron
January 2013
Coronary Revascularization in Ischemic Heart Failure Patients: A Rapid Review. January 2013; pp. 1–28.
Coronary Revascularization in
Ischemic Heart Failure Patients:
A Rapid Review
G Pron
January 2013
Risultati
PARR-2 : 1 anno riduzione non significativa di ospedalizzazione e
morte cardiaca;
HEART : primo RCT cha ha messo a confronto PCI e CABG con terapia
medica, non differenza significativa di sopravvivenza a 5 anni tra i due
gruppi;
STICH : mortalità a 4 anni ridotta non significativamente nell’analisi
ITT, riduzione significativa nell’analisi as treated e per protocol.
Non vantaggi in termini di sopravvivenza per CABG + SVR
3/31/2015
10
Meta-Analysis24 Studies 3088 Patients
Allman JACC 2002
20
15
10
5
0Revasc. Medical Revasc. Medical
Viable Non-Viable
Death rate
%/yr
-79.6%
X2=147
P<0.0001
23.0%
X2=1.43
P<0.23
Randomized3/31/2015
11
STICH Trial
• Randomized
• 127 Clinical Sites
• 1212 patients
• Medical therapy (602 pts)
• Medical therapy plus CABG (610 pts)
• Inclusion criteria
• CAD amenable to CABG
• LVEF < 35%
• Primary endpoint
• Death from any cause
3/31/2015
12
1.0
0.8
0.6
0.4
0.2
00 1 2 3 4 5 6
Pro
ba
bili
ty o
f D
ea
th A
ny C
au
se
Years since Randomization
CABG
Velazquez et al.: N ENGL J MED 364;17, April 28, 2011
HR 0.86 95% CI (0.72-1.04) P=0.12
MortalityIntent to Treat Analysis
Med
STICH TrialAs Treated
• CABG and OMT
• 610 patients assigned
• 555 (91%) underwent CABG
• OMT
• 602 patients assigned
• 100 (17%) crossed over to CABG
3/31/2015
11
STICH Trial
• Randomized
• 127 Clinical Sites
• 1212 patients
• Medical therapy (602 pts)
• Medical therapy plus CABG (610 pts)
• Inclusion criteria
• CAD amenable to CABG
• LVEF < 35%
• Primary endpoint
• Death from any cause
3/31/2015
12
1.0
0.8
0.6
0.4
0.2
00 1 2 3 4 5 6
Pro
ba
bili
ty o
f D
ea
th A
ny C
au
se
Years since Randomization
CABG
Velazquez et al.: N ENGL J MED 364;17, April 28, 2011
HR 0.86 95% CI (0.72-1.04) P=0.12
MortalityIntent to Treat Analysis
Med
STICH TrialAs Treated
• CABG and OMT
• 610 patients assigned
• 555 (91%) underwent CABG
• OMT
• 602 patients assigned
• 100 (17%) crossed over to CABG
3/31/2015
13
1.0
0.8
0.6
0.4
0.2
00 1 2 3 4 5 6
Mo
rtalit
y R
ate
Years Following Randomization
Med
MortalityAs Treated Analysis (During Year 1)
CABG
HR 0.70 95% CI(0.58, 0.84) P<0.001
Velazquez EJ et al.: N Engl J Med 2011;364:1607-16. Supplement
40 paz FU @ 30 gg
La rivascolarizzazione completa è
associata a sopravvivenza superiore.
La rivascolarizzazione incompleta è
associata a pregresso IMA, EF depressa,
malattia trivasale.
3/31/2015
4
Observational
Revascularization of
Viable Myocardium
LV Function
3/31/2015
4
Observational
Revascularization of
Viable Myocardium
LV Function
3/31/2015
5
Improvement in LV FunctionPET
N 35
Inclusion
CHF
CAD
Impaired LVF
LVEF 23 + 7%
Pagano et al, JTCVS: 1998
3/31/2015
6
Improvement in LV FunctionPET
2 4 6 8 16
40
30
20
10
0
-100
∆ EF
10 12 14
PET Viable Segments
Revascularization of
Viable Myocardium
Quality of Life
3/31/2015
5
Improvement in LV FunctionPET
N 35
Inclusion
CHF
CAD
Impaired LVF
LVEF 23 + 7%
Pagano et al, JTCVS: 1998
3/31/2015
4
Observational
Revascularization of
Viable Myocardium
LV Function
3/31/2015
7
Functional Status and Quality of Life
N 63
Inclusion
CAD
LV Dysfunction
CHF main symptom
LVEF 28%
NYHA FC 2.6 +/- 0.7
CABG 100%
Marwick et al, JACC: 1999
3/31/2015
6
Improvement in LV FunctionPET
2 4 6 8 16
40
30
20
10
0
-100
∆ EF
10 12 14
PET Viable Segments
Revascularization of
Viable Myocardium
Quality of Life3/31/2015
8
Change in Exercise Capacity
PET
20 40 60 80 100
PET viable (%)
80
60
40
20
0
-20
-40
-600
De
lta
ME
TS
(%
)
Marwick et al, JACC: 1999
Revascularization of
Viable Myocardium
Survival
3/31/2015
7
Functional Status and Quality of Life
N 63
Inclusion
CAD
LV Dysfunction
CHF main symptom
LVEF 28%
NYHA FC 2.6 +/- 0.7
CABG 100%
Marwick et al, JACC: 1999
3/31/2015
9
Meta-Analysis24 Studies 3088 Patients
Age 61
Male 70%
LVEF 33%
NYHA FC 2.8
+ Viability 42%
Revascularization 35%
F/U 25 months
Allman et al, JACC: 2002
3/31/2015
8
Change in Exercise Capacity
PET
20 40 60 80 100
PET viable (%)
80
60
40
20
0
-20
-40
-600
De
lta
ME
TS
(%
)
Marwick et al, JACC: 1999
Revascularization of
Viable Myocardium
Survival
3/31/2015
10
Meta-Analysis24 Studies 3088 Patients
Allman JACC 2002
20
15
10
5
0Revasc. Medical Revasc. Medical
Viable Non-Viable
Death rate
%/yr
-79.6%
X2=147
P<0.0001
23.0%
X2=1.43
P<0.23
Randomized
3/31/2015
16
STICH Trial
• Anatomic Characteristics
• Prognostic Factors
• 3V CAD
• LVEF < mean (27%)
•ESVI > mean (79 ml/m2)
• Patients assigned
• 0-1 prognostic factors
• 2-3 prognostic factors
3/31/2015
18
Schematic Representation of the Clinical
Implications of the Present Study Findings
Panza et al.: JACC VOL . 64 , NO. 6, AGUST 12 , 2014: 553 – 61
Summary
• Patients with LV Dysfunction can benefit
from revascularization
• Viability is important
• No viability does not eliminate benefit of
revascularization
• Extent of CAD
• LVEF
• LV size
• Patients at greatest risk appear to derive
greatest benefit
3/31/2015
16
STICH Trial
• Anatomic Characteristics
• Prognostic Factors
• 3V CAD
• LVEF < mean (27%)
•ESVI > mean (79 ml/m2)
• Patients assigned
• 0-1 prognostic factors
• 2-3 prognostic factors
3/31/2015
17
MortalityPatients with 0 or 1 Prognostic Factors
0.5
0.4
0.3
0.2
00 1 2 3 4 5 6
Dea
th R
ate
Years from Randomization
Panza et al.: JACC VOL . 64 , NO. 6, AGUST 12 , 2014: 553 – 61
0.1
CABG
Med
N = 576
Treatment Hazard Ratio 95% CI P-value
CABG: MED 1.08 0.81, 1.44 0.591
0.5
0.4
0.3
0.2
00 1 2 3 4 5 6
De
ath
Ra
te
Years from Randomization
Panza et al.: JACC VOL . 64 , NO. 6, AGUST 12 , 2014: 553 – 61
0.1
CABG
Med
N = 636
MortalityPatients with 2 or 3 Prognostic Factors
Treatment Hazard Ratio 95% CI P-value
CABG: MED 0.71 0.56, 0.89 0.004
3/31/2015
17
MortalityPatients with 0 or 1 Prognostic Factors
0.5
0.4
0.3
0.2
00 1 2 3 4 5 6
De
ath
Ra
te
Years from Randomization
Panza et al.: JACC VOL . 64 , NO. 6, AGUST 12 , 2014: 553 – 61
0.1
CABG
Med
N = 576
Treatment Hazard Ratio 95% CI P-value
CABG: MED 1.08 0.81, 1.44 0.591
0.5
0.4
0.3
0.2
00 1 2 3 4 5 6
Dea
th R
ate
Years from Randomization
Panza et al.: JACC VOL . 64 , NO. 6, AGUST 12 , 2014: 553 – 61
0.1
CABG
Med
N = 636
MortalityPatients with 2 or 3 Prognostic Factors
Treatment Hazard Ratio 95% CI P-value
CABG: MED 0.71 0.56, 0.89 0.004
LVEDP
Rivascolarizzazione…HF
CABG… e la PCI ?
REVIVED-BCIS2 study protocol Version 7 1st May 2015 6/49
ISRCTN45979711 / NCT01920048
Major Exclusion Criteria
Acute myocardial infarction < 4 weeks prior to randomisation (clinical definition)
Decompensated heart failure requiring inotropic support <72 hours prior to randomisation
Any contraindication to PCI
Sample Size and Enrolment
n=700
Start date: 1st June 2013
Recruitment start date: 1st September 2013
Recruitment end date: 1st March 2017
Follow-up end date: 1st March 2019
Number of centres: 30-35 (listed in appendix 1)
1.2. Trial Flowchart
LVEF ∆ 35%
Extensive CAD
Viability in at least 4 dysfunctional
segments
Suitable for PCI
RANDOMISE
OMT PCI + OMT
Clinical f/u (6 months, 1 yr, 2 yr then yearly
telephone f/u)
Echo at 6 months and 1 yr
ICD f/u at 6 months,1 yr and 2 yrs
Meets other eligibility
criteria
REVIVED-BCIS2 study protocol Version 7 1st May 2015 6/49
ISRCTN45979711 / NCT01920048
Major Exclusion Criteria
Acute myocardial infarction < 4 weeks prior to randomisation (clinical definition)
Decompensated heart failure requiring inotropic support <72 hours prior to randomisation
Any contraindication to PCI
Sample Size and Enrolment
n=700
Start date: 1st June 2013
Recruitment start date: 1st September 2013
Recruitment end date: 1st March 2017
Follow-up end date: 1st March 2019
Number of centres: 30-35 (listed in appendix 1)
1.2. Trial Flowchart
LVEF ∆ 35%
Extensive CAD
Viability in at least 4 dysfunctional
segments
Suitable for PCI
RANDOMISE
OMT PCI + OMT
Clinical f/u (6 months, 1 yr, 2 yr then yearly
telephone f/u)
Echo at 6 months and 1 yr
ICD f/u at 6 months,1 yr and 2 yrs
Meets other eligibility
criteria
Conclusioni…
v I pazienti con disfunzione ventricolare sn possono beneficiare della
rivascolarizzazione
v Importante la ricerca e la dimostrazione della vitalità miocardica
v “Miocardio ibernato”
v L’assenza di vitalità non esclude i benefici della rivascolarizzazione
v Estensione della malattia coronarica, Tronco Comune,
v LVEF – volumi del LV
v Il beneficio maggiore è per i pazienti a più alto rischio
v Studi che confrontano PCI e terapia medica potranno dimostrare
maggiore beneficio in termini di rivascolarizzazione
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