Ruolo della rivascolarizzazione miocardica nello scompenso ...extent of irreversibly damaged...

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

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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

by guest on September 6, 2015http://circ.ahajournals.org/Downloaded from


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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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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

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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

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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

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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

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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

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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


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


• 100 (17%) crossed over to CABG

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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

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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


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


• 555 (91%) underwent CABG

• OMT


• 100 (17%) crossed over to CABG

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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.

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Observational

Revascularization of

Viable Myocardium

LV Function

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Observational


Viable Myocardium

LV Function

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Improvement in LV FunctionPET

N 35

Inclusion

CHF

CAD

Impaired LVF

LVEF 23 + 7%

Pagano et al, JTCVS: 1998

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2 4 6 8 16

40

30

20

10

0

-100

∆ EF

10 12 14

PET Viable Segments


Viable Myocardium

Quality of Life

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5


N 35

Inclusion

CHF

CAD

Impaired LVF

LVEF 23 + 7%

Pagano et al, JTCVS: 1998

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Observational


Viable Myocardium

LV Function

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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

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2 4 6 8 16

40

30

20

10

0

-100

∆ EF

10 12 14

PET Viable Segments


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

(%

)



Viable Myocardium

Survival

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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%


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Age 61

Male 70%

LVEF 33%

NYHA FC 2.8

+ Viability 42%

Revascularization 35%

F/U 25 months

Allman et al, JACC: 2002

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Change in Exercise Capacity

PET

20 40 60 80 100

PET viable (%)

80

60

40

20

0

-20

-40

-600

De

lta

ME

TS

(%

)



Viable Myocardium

Survival

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10


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

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STICH Trial

• Anatomic Characteristics

• Prognostic Factors

• 3V CAD

• LVEF < mean (27%)

•ESVI > mean (79 ml/m2)

• Patients assigned

• 0-1 prognostic factors


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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

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STICH Trial

• Anatomic Characteristics

• Prognostic Factors

• 3V CAD

• LVEF < mean (27%)

•ESVI > mean (79 ml/m2)

• Patients assigned



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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


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



0.1

CABG

Med

N = 636



CABG: MED 0.71 0.56, 0.89 0.004

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0.5

0.4

0.3

0.2

00 1 2 3 4 5 6

De

ath

Ra

te



0.1

CABG

Med

N = 576


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



0.1

CABG

Med

N = 636



CABG: MED 0.71 0.56, 0.89 0.004

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

Ruolo della rivascolarizzazione miocardica nello scompenso ...extent of irreversibly damaged...

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