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Vulnerable or High Risk Plaque Multimodality Plaque Imaging 1. Plaque Progression - Nomenclature, 1990 -1995 2. Plaque Imaging - Invasive / Non-Invasive 1995 -2010 3. HRP Bioimage Study - Disease Burden 2010 -2012 4. The Two Extreme Paradox 2012 -2020

Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

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Page 1: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

Vulnerable or High Risk Plaque Multimodality Plaque Imaging

1. Plaque Progression - Nomenclature, 1990 -1995

2. Plaque Imaging - Invasive / Non-Invasive 1995 -2010

3. HRP Bioimage Study - Disease Burden 2010 -2012

4. The Two Extreme Paradox 2012 -2020

Page 2: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque
Page 3: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

J-F Toussaint, V Fuster et. al. ATVB.1995;15:1533V Fuster et al., NEJM 1992; 326:242 –326:310V Fuster, Circ 1994; 90:2126 - AHA Report Circ 1995; 92:1355 E Falk, PK Shah, V Fuster Circ 1995;92:657-

Mechanisms Leading to Myocardial Infarction: InsightsFrom Studies of MRI (Autpsy) & Vascular Biology

Page 4: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

PHASE 4

I-III

PHASE 1 PHASE 2

PHASE 3

PHASE 5Acute SyndromesMyocardial infarctionUnstable anginaIschemic sudden death

No Symptoms

IV-Va

VI

VI

Vb-Vc

V Fuster et al., NEJM 1992; 326:242 –326:310 - Vulnerable Plaque (JM) - HRP (VF)V Fuster, Circ 1994; 90:2126 - AHA Report Circ 1995; 92:1355 (modified)E Falk, PK Shah, V Fuster Circ 1995;92:657- J-F Toussaint, V Fuster et. al. ATVB.1995;15:1533

Anginapectoris

PHASE 4VI

Plaques, Autopsy / Imaging 1990 -1995

Page 5: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

Vulnerable or High Risk Plaque Multimodality Plaque Imaging

1. Plaque Progression - Nomenclature, 1990 -1995

2. Plaque Imaging - Invasive / Non-Invasive 1995 -2010

3. HRP Bioimage Study - Disease Burden 2010 -2012

4. The Two Extreme Paradox 2012 -2020

Page 6: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

1995-2005 Expedition, 2005-2010 Consolidation

R Corti, V Fuster EHJ. 2011 (April 19)

Page 7: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

CONFIDENTIAL – Oct 9, 2007

Morphological Imaging,1995-2010

MM Sadeghi, ZA Fayad et. al. J Nucl Med 2010; 51:51S

Page 8: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

Vulnerable or High Risk Plaque Multimodality Plaque Imaging

1. Plaque Progression - Nomenclature, 1990 -1995

2. Plaque Imaging - Invasive / Non-Invasive 1995 -2010

3. HRP Bioimage Study - Disease Burden 2010 -2012

4. The Two Extreme Paradox 2012 -2020

Page 9: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

1b). PESA & AWHS 1a). HRP > 55y,40-54y, n= 8,000 , FU 0,3,6 y N=7000 FU 3y

Omics (Copenhagen, Duke, HRP, Framingham)Telomere (S.blot, qPCR, Fresh)

Predictive ?Economics ?

Life Style & Imaging ?

Page 10: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

CARDIOVSCULAR RISK FACTORS (7) & LIFE STYLE

>2 Risk Factors

1. MI & 2. Stroke

25% in 10 Yrs

75% in 30 Yrs

3. DBD & 4. AD Quality

Framingham (2010) 5, Interheart (2004)2:Obesity, Sedentary(Diet)

c

c

Page 11: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

HRP - Bioimage Initiative 2008 - 2012

– Largest industry funded biomarker initiative ever

– Unique structure of collective funding, design, oversight, and interpretation, while study execution is done by a third-party

– HRP Initiative extended through • Copenhagen Heart Studies (CCHS and

CGPS)• Framingham Heart Study under

NIH/NHLBI CRADA

PI: V. Fuster, Co-PI: E. Falk, P. Muntendam - AHJ 2010;160:49

Page 12: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

HRP - Bioimage Iniciative - Steering Committee

Valentin Fuster, MD, PhD (Chair) Carol McCall, FSA, MAAAErling Falk, MD, PhD (Co-Chair) Pedro R. Moreno, MDJuan José Badimon, PhD B.G. Nordestgaard, MD, PhDMat Daemen, MD, PhD James H.F. Rudd, MD, PhDZahi A. Fayad, PhD Prediman K. Shah, MDMario Garcia, MD Henrik Sillesen, MDGeoffrey S. Ginsburg, MD Anton van der Steen, PhDStanley L. Hazen, MD, PhD Prof. Sir Magdi M. YacoubSpencer B. King, III, MD Chun Yuan, PhD

BG Medicine (Peter Muntendam) & Humana (Carol McCall)

Page 13: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

HRP - BioImage Study - 63% > 2 Risk Factors

PI: Valentin Fuster, Co-PI: Earling Falk, Peter Muntendam - AHJ 2010;160:49

Page 14: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

H Sillesen, V Fuster et. al. JACC Cardiovasc Img 2012 (In Press).

HRP-Bioimage: Overlap Of Imaging Modalities

Page 15: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

First Mobile 3T at WorkHRP - BioImage Study – Mobile Units

PI: Valentin Fuster, Co-PI: Erling Falk, Peter Muntendam - AHJ 2010;160:49

Page 16: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

Carotid Plaque Burden, cm2

3D US Manual (Sweep 2D) vs 3D Transducer

Focal structure into the arterial lumen of at least 0.5 mm or 50% of surrounding IMT value. 37% missed at Clasical 2D

CardioSCORE - R7 - ApoA1, Apo B, B2M, CEA, CRP, Lp(a),Transferrin

H Sillesen, V Fuster et. al JACC Imag 2012 (In Press).

Page 17: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

PHASE 1 - PLAQUE BURDEN - 3D US SWEEP PRIMARY EVENTS - N=186, 18 MONTHS

Variables OR (95% CI) P value Chi-square

Burden, > 4.20 cm2 3.63 (2.26-5.82) <0.0001 28.5

Burden, 2.58-4.20 cm2 1.83 (1.09-3.05) 0.022 5.3

Burden, 0.01-2.57 cm2 1.15 (0.65-2.00) 0.64 0.2

H Sillesen, E Falk, P Muntendam, V Fuster, JACC Img 2012 (Subm)

Page 18: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

(n = 1456) (n = 1456) (n = 1457) (n = 1454)

PHASE 1 - COMPARATIVE PREVALENCE BETWEEN DEGREE OF CACAND DEGREE OF CAROTID PLAQUE BURDEN BY 3D SWEEP

IMT vs CAC: +Ilio-Femoral: +++

U Baber, R Mehran, P Muntendam, M Garcia, H Sillesen, E Falk, V Fuster, 2012

Page 19: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

PHASE 2 - BIOLMAGE (3D-US & CAC) & CardioSCORE-R7 Events By December 2011

Acute MI 17%

IschemicStroke18%Coronary

Revasc. 16%

Death 27%

P Muntendam, E Falk, V Fuster 2012

Page 20: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

PHASE 2 – BioImage (CACD-3DUS) & CardioScore Significant Risk Prediction For 1ary Events

0

0.01

0.02

0.03

0.04

0.05

0.06

0.07

0.08

0.09

0.1

0 100 200 300 400 500 600 700 800

Time (days)

Cum

ulat

ive In

ciden

ce

> 400 101-400 1-100 0

0

0.01

0.02

0.03

0.04

0.05

0.06

0.07

0.08

0.09

0.1

0 100 200 300 400 500 600 700 800

Time (days)

Cum

ulat

ive In

ciden

ce> 230 mm3 70-230 mm3< 70 mm3none detected

0

0.01

0.02

0.03

0.04

0.05

0.06

0.07

0.08

0.09

0.1

0 100 200 300 400 500 600 700 800

> 5.8 4.7-5.7 3.6-4.6< 3.5

Time (days)

Cum

ulat

ive In

ciden

ce

CACS 3D carotid ultrasound CardioSCORE blood test

N=3557 for all plots that have 3D carotid US

Cumulative Event Rate by Category

P Muntendam, E Falk, V Fuster 2012 How Much Risk Prediction Is Added To The Frs ?

Page 21: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

PHASE 2 – BioImage (3D-US & CAC) Significant Added Risk Prediction For 1ary Events

P Muntendam, E Falk, V Fuster 2012 How Much Risk Prediction Is Added To The Frs ?

Page 22: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

PHASE 2 – CardioScore Significant Added Prediction to FRS at 1ary Events

26 48 56

The Sensitivity of Detection Increases From 26% for FRS alone to 56% with the combination

Page 23: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

1b). PESA & AWHS 1a). HRP > 55y,40-54y, n= 8,000 , FU 0,3,6 y N=7000 FU 3y

Omics (Copenhagen, Duke, HRP, Framingham)Telomere (S.blot, qPCR, Fresh)

Predictive ?Economics ?

Life Style & Imaging ?

Page 24: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

Vulnerable or High Risk Plaque Multimodality Plaque Imaging

1. Plaque Progression - Nomenclature, 1990 -1995

2. Plaque Imaging - Invasive / Non-Invasive 1995 -2010

3. HRP Bioimage Study - Disease Burden 2010 -2012

4. The Two Extreme Paradox 2012 -2020

Page 25: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

TRIAL MVD DM INTERV. MT. EP.

SYNTAX + - ++ - ++

BARI - + + + +

FREEDOM + + ++ + +

1. COMPLEX CHRONIC CORONARY DISEASE

DataRevascul. <CABG

Sx Sc. (Reg ) <CABG

Ischemic Score

Intervent. = MT SxSc <CABG, Xov.42%

Intervent. = MT Ischemic Score

FREEDOM Score (3)Risk Frs 80% - PolypillNon Invasive Imaging

FAME - - + - +

COURAGE - - + + +

Conclusions Methods-Interests Concerns: Risk Frs.-Rx

Page 26: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

1. MEETING TARGETS FOR RISK FACTOR CONTROL?Risk Factors - Proportion of Participants at Goal % – 1 yearTrials LDL SBP DBP Hb A1C

Meet Goals

Base FUBARI-

2D 75 56 70 5214 20

COURAGE 51 55 55 5912 19

FREEDOM 55 63 53 5512 20

Freedom, Bari-2D, Courage Investigators, 2012 (Subm.)PURE (S Yusuf et al.) Lancet 2011; Aug 28 - Poor Countries,7% !!!NHANES, AHA, NHLBI-JNC-7, NHLBI-NCEP P Muntner, V Fuster et al., AHJ 2011; 161: 719 – 49 seconds !!!!

Page 27: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

FOOD INTERACTION

PHARMACOKINETIC INTERACTION WITH

ASPIRIN

PHARMACOKINETIC INTERACTION WITH

SYMVASTATIN

PHARMACOKINETIC INTERACTION WITH

RAMIPRIL

PHARMACODYNAMIC INTERACTION WITH ASPIRIN

PHARMACODYNAMIC INTERACTION WITH

SYMVASTATIN

PHARMACODINAMIC INTERACTION WITH

RAMIPRIL

BIO-EQUIVALENCE

FOCUS 1General

Adherence

FOCUS 2Polypill

Adherence

ArgentinaBrazilParaguay

ItalySpain

ASA, Statin, ACE-Inhibitor

1. POLYPILL CNIC-FERRER: ADHERENCE – ECONOMICS

G Sanz, V Fuster Am. H J 2011;162:811 – Semin. Thor. Cardiov 2011;23:24

Page 28: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

Molecular Imaging – PEN – 2011-2015NIH Program of Excellence in Nanotechnology

HHSN2682010000045C$16,447,515 – 5 years

Zahi Fayad, MSSM Valentin Fuster, MSSM Roger Hajjar, MSSM Martin Schwarz, MSSMRobert Langer, MITOmid Farokhzad, BrighamEdward A. Fisher, NYUIra Tabas, Columbia

1 Genetics (SIRCA) / Stem Cell Rx. 2010 (Subm), Fibrosis3. Radiology 2010; 256:774 - Feo-MRI, Gold-Micro CT, MPI 2. Molecular Pharmaceutics 2010, Oct 28 – Corticoid Rx

Page 29: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

Sj Nicholis et al JACC 2006;47:992 M Lobatto, V Fuster, ZA Fayad, W Mulder. Molec Pharmac 2010;7:20.Liposome encapsulated Prednisolone M Lobatto, V Fuster, ZA Fayad, W Mulder. Nat Rev Drug Discov 2011;10:963.rHDL Nanoparticles Statin Loaded

Biological Imaging & Local Treatment

Rx

Page 30: Vulnerable or High Risk Plaque Multimodality Plaque Imaging · Vulnerable or High Risk Plaque Multimodality Plaque Imaging ... Mario Garcia, MD ... Vulnerable or High Risk Plaque

Vulnerable or High Risk Plaque Multimodality Plaque Imaging

1. Plaque Progression - Nomenclature, 1990 -1995

2. Plaque Imaging - Invasive / Non-Invasive 1995 -2010

3. HRP Bioimage Study - Disease Burden 2010 -2012

4. The Two Extreme Paradox 2012 -2020