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  • .

  • 21

  • 21

  • =

  • ,

    ..

    ( (99-55 ..)

    De Rerum Natura (,(" "), ) , char. 5, I. 1007

  • Bertel Thorvaldsen

    1844.

    James B. Herrick, JAMA. 1983;250(13):1757-1762

  • Karl von Rokitansky :

    Karl von Rokitansky, Manual of Pathological Anatomy 1852

    Karl von Rokitansky

  • Rudolf Virchow :

    Virchow Rudolf. Gesammelte Abhandlungen zur Wissenschatflichen Medizin.

    Frankfurt: Meidinger Sohn & Co., 1856: 458636.

    .

  • 1872

    Georg Eduard von Rindfleisch( )

    Rindfleisch E. A Manual of Pathological Histology. vol 1.

    London, England: New Sydenham Society; 1872

    http://en.wikipedia.org/wiki/File:Eduard_von_Rindfleisch_3.png

  • 1876

    W Kster ( )

    Kster W. Endarteritis and arteritis Berlin Klin Wschr 1876;13:454-455

  • Marchand Felix( /)

    ,

    Marchand Felix, Ueber Atreriosklerose, Verh. Kongr. Inn. Med., 21:23, 1904

    .

  • 1909

    Alexander Ignatowski( )

    Ignatowski, A. (1908) Influence de la nourriture animale sur

    l'organisme des lapins. Arch. Med. Exp. Anat. Pathol. 20: 1-20

  • 1913

    Nikolay Anitschkow( )

    Anitschkow N, Chalatow S. Ueber experimentelle Cholester-insteatose und ihre

    Bedeutung fuer die Entstehung einiger pathologischer Prozesse. Zentrbl Allg Pathol

    Pathol Anat 1913;24:19.

  • Aschoff L. Aufbau derMenschlichen Thromben und das Vorkommen von Plauttchen

    in den blutbildenen Organen. Virchows Arch Path Anat 1924; 130: 93144.

    1924

    Ludwig Aschoff( )

  • JB Duguid( )

    -

    Duguid, JB : The Journal of Pathology and Bacteriology, Volume 58, Issue 2, pages

    207212, April 1946

  • To 1987 Seymour Glacov (1925-2008)

    ,

    .

    Glagov S et al NEJM 1987;316:1371-5

  • 21

  • 21

  • 21

  • MA

    CE

    (%

    )

    Years0 1 2 3

    (CL)

    (NCL)

    0

    5

    10

    15

    20

    25

    12.9%

    27.2%

    11.6%

    2.7%

    Stone GW et al., N Engl J Med 2011;364:226-35

    J Am Coll Cardiol Img 2012;5:S95105

    .

    PROSPECT 3,4 ys FU n=697 ACS pts with successful PCI in 1 or 2

    major vessels

  • JA Schaar, JE Muller, E Falk, R Virmani, V Fuster, PW Serruys, A Colombo, C Stefanadis,

    SW Casscells, PR Moreno, A Maseri and A F.W van der Steen, , Eur Heart J 2004;25:1077-1082

    Report of a Meeting on the Vulnerable Plaque, June 17 and 18, 2003, Santorini, Greece

    Circulation. 2003 Oct 14;108(15):1772-8

  • 21

  • STEMI 3 .EC Keeley et al, Am J Cardiol. 2014 May 15;113(10):1621-7

    &

    HORIZONS AMI

    : ,

    , ,

    , )

    3,137 patients with

    STEMI who

    underwent primary

    PCI in a single

    coronary artery

  • JM Cheng et al., European Heart Journal

    (2014) 35, 639647

    12 .

    ATHEROREMO-IVUS study

    VH-IVUS of a non-culprit coronary

    artery was performed in 581 patients

    who underwent coronary angiography

    for ACS (n=318) or stable angina

    (n=263). Primary endpoint was MACE

    defined as mortality, ACS, or unplanned

    coronary revascularization

    Large TCFA : plaque burden of 70%

  • 21

  • olmesartan (20 mg/day) valsartan (80

    mg/day) 6 , VUS

    .

    - &

    H Ishii et al, Am J Cardiol. 2013 Apr 24

    100 stable CAD pts who

    underwent PCI were

    randomly selected to

    receive 1 of the 2

    angiotensin II

    receptor blockers.

    Nontarget coronary lesions

    with mild to moderate

    stenosis were measured by

    IVUS at baseline and

    after 6 ms.

    p

  • placebo 9 .

    &

    M Christoph et al, Heart Vessels. 2014 Feb 12

    86 non-culprit lesions in 54 non-diabetic pts with

    ACS were observed in a 9-month prospective,

    double-blind, and placebo-controlled IVUS study.

    Pts were randomized to receive either 30 mg

    pioglitazone or placebo.

    Agonist of peroxisome proliferator-activated receptor c (PPAR) used for the treatment of type 2 diabetes (ACTOS)

  • Stent vProtect Luminal Shield - SECRITT I trial

    (Santorini Criteria for Investigating and Treating Thin Capped Fibroatheroma)

    V Protect Luminal Shield i stent

    . ,

    (56-m)

    .

    n=29 pts with

    known vulnerable

    plaques (IVUS &

    OCT) randomized to

    be treated either

    with vProtect device

    or with optimal

    therapy

    Angiographic FU at

    6 mths 16 pts

    with good results

    Wykrzykowska JJ,,PW Serruys, EuroIntervention 2012 Dec 20;8(8):945-54

    0,00

    10,00

    20,00

    30,00

    40,00 33,20

    18,70

    % stenosis

    Baseline

    6 months

  • 21

  • &

    J Narula et al , J Am Coll Cardiol 2013;61:104151

    , (TCFA)

    .

    295

    213

    p < 0.001

    0,00

    1,00

    2,00

    3,00

    4,00

    5,00

    1,332,26

    4,37

    Necrotic core size (mm2)

    Stable

    TCFA

    Rupture

  • 21

  • -6,8

    2,8

    -8

    -6

    -4

    -2

    0

    2

    4

    Change in lipid volume index (%)

    Pitavatsatin

    Diet

    &

    K Hattori et al, JACC Cardiovasc Imaging. 2012 Feb;5(2):169-77

    Prospective serial

    OCT & IVUS of

    nontarget lesions was

    performed in 42

    stable angina pts

    undergoing elective

    PCI. 26 received 4 mg

    pitavastatin, 16

    dietary modification

    alone. FU 9 mths

    (median interval)

    9

    .

    p= 0,04

  • &

    YELLOW

    Kini AS et al, J Am Coll Cardiol 2013;62:219

    NIRS

    .

    87 pts with multivessel CAD

    undergoing PCI and at least 1

    other severely obstructive

    nontarget lesion to intensive

    (rosuvastatin 40 mg daily) or

    standard-of-care lipid-lowering

    therapy were evaluated at

    baseline and after 7 weeks of

    therapy with FFR, NIRS &

    IVUS.

    -24,4

    5,4

    -25

    -20

    -15

    -10

    -5

    0

    5

    10

    Change in lipid core burden index (%)

    Rosuvastatin

    Standard

    therapyLCBI : Yellow pixels within the analyzed segment divided by all viable pixels.

  • 21

  • &

    .

    Remodelling index

    (RI): lesion/reference

    external elastic

    membrane area

    47 patients with

    stable angina and

    ACS who underwent

    culprit vessel PCI

    p < 0.001

    S. Rathore et al , Atherosclerosis 221 (2012) 405 415

    0

    20

    40

    60

    80

    100

    47,86

    74,41

    Axis Title

    Fibrous cap thickness (m)

    PR group

    non-PR group

  • &

    .

    Toutouzas K, Stefanadis C, Am Heart J. 2011 Jun;161(6):1192-9

  • 0

    10

    20

    30

    40

    50

    60

    43,0056,00

    Axis Title

    Fibrous cap thickness (m)

    Ruptured culprit

    TCFA

    .

    & 126 plaques from

    82 ACS pts.

    Fibrous cap

    thickness was

    determined by

    OCT.

    p

  • 21

  • &

    9

    .

    K Hattori et al, JACC Cardiovasc Imaging. 2012 Feb;5(2):169-77

    Prospective serial

    OCT & IVUS of

    nontarget lesions was

    performed in 42

    stable angina pts

    undergoing elective

    PCI. 26 received 4 mg

    pitavastatin, 16

    dietary modification

    alone. FU 9 mths

    (median interval)

    Baseline

    9 months

    0

    50

    100

    150

    200

    PitavastatinDiet

    140140

    189

    142 Baseline

    9 months

  • 21

  • & (strain)

    PF Zhang et al, Int J Cardiovasc Imaging (2011) 27:3949

    .

    7 minipigs fed with

    atherogenic diet for

    40 ws.

    Endothelium of one side

    of the renal arteries

    denuded at 5th wk.

    Strain calculated from 2

    IVUS images acquired

    in situ.

    16 elastograms matched

    well with corresponding

    histological slices.

    p

  • ,

    .

    Fatty atheromatic plaque with low

    echogenicity, provoking 80% stenosis.

    DT : 1,3C

    Toutouzas K,,Stefanadis C, J Am Coll Cardiol. 2012 May 1;59(18):1645-53

  • 21

  • & -

    -

    .Toutouzas K,., Stefanadis C, Int J Cardiol. 2007 Jul 31;119(3):368-73

    N=100 pts

    p

  • DT

    (C

    )

    ACS SA

    No Statins

    Statins

    n=256 pts

    &

    Stefanadis et al, Atherosclerosis 2007 Jun;192(2):396-400

    ,

    .

    N=100 pts

    p

  • (Aliskiren) &

    Aliskiren ( )

    64%

    .S Kuhnasta et al., Journal of Hypertension 2012, 30:107116

    Aliskiren administered

    for 14 weeks in mice

    with vulnerable or stable

    plaques

    p< 0,001

    p

  • &

    follow-up 3 ( ).SM Nidorf et al, J Am Coll Cardiol 2013;61:40410

    532 pts with stable

    CAD receiving

    aspirin and/or

    clopidogrel and

    statins randomly

    assigned to

    colchicine

    0.5 mg/day or no

    colchicine and

    followed for a

    median of 3 years.

    p< 0,001

    p

  • 21

  • 0

    5

    10

    15

    20

    25

    30

    Vasa Vasorum

    13

    26

    Stable TCFA

    TCFA vasa vasorum

    .

    F Kolodgie et al, J Am Coll Cardiol 2007;49:2093101

    Vasa vasorum (TCFA)

    ( )

  • .J Sluimer, F Kolodgie et al, J Am Coll Cardiol 2009;53:151727

    Vasa vasorum

    ( )

    n=28 coronaries

    IT intimal thickening normal

    PIT pathological intimal

    thickening

    E-FA early thick fibrous cap

    atheroma

    L-FA late fibrous cap atheroma

    TCFA thin fibrous cap

    atheroma

    RPT rupture

  • IVUS vasa vasorum

    IVUS vasa vasorum

    &

    Vavuranakis M,..,Stefanadis C, International Journal of Cardiology 130 (2008) 2329

    vasa vasorum

    IVUS( )

  • 21

  • VEGF production

    inhibitor

    & ( )

    n=24 swine

    (LAD)

    VV assessment

    by micro-CT

    p

  • Avastin

    Mic

    roves

    sels

    per

    mm

    Control

    bevacizumab

    .

    4 stent

    Stefanadis C, , Kipshidze N, Atherosclerosis 2007, Vol.195:2;269-76

  • First-in-man Study

    Avastin eluting BiodivYsio stent

    Follow-up 2

    . To Avastin-stent

    , 4

    > 1 mm2.

    Stefanadis C, , Kipshidze N, EuroIntervention. 2008 Jan;3(4):460-4

  • First-in-man Study

    Avastin eluting BiodivYsio stent

    Follow-up 8

    0%

    20%

    40%

    60%

    80%

    100%

    12

    34

    56

    78

    100%95%

    90%90%

    85%80%

    80%80%

    follow-up 8 , 80%

    .

    C Stefanadis et al, in press

  • BMS

    S Deftereos, .,C Stefanadis, MW Cleman, J Am Coll Cardiol 2013;61:167985

    BMS

    placebo.

    n=196 pts with DM

    underwent PCI with a

    BMS, were randomized to

    receive colchicine 0.5 mg

    twice daily or placebo for

    6 months. Restenosis and

    neointima formation were

    studied with angiography

    and IVUS after 6 months

  • 21

  • CT

    M Kashiwagi et al, Atherosclerosis 212 (2010) 171176

    CT.

    n=73 pts with SA who

    underwent MDCT.

    2 monocyte subsets

    were measured by flow

    cytometry.

    NCP vulnerability

    defined according to the

    presence of positive

    remodeling and/ or low

    CT attenuation plaques

    p

  • PROSPECT

    3

    .

    S Inaba et al,, J Am Coll Cardiol Img 2014;7:708

    n= 697 ACS pts

    underwent 3-vessel

    gray-scale and

    IVUS-VH; 3,223

    NCLs were

    identified by IVUS.

    Remodeling index

    (RI) : external elastic membrane area at the MLA site divided by the average

    of the proximal and distal reference external elastic membrane areas.

  • 21

  • &

    (-3.0%)

    .P Schoenhagen et al, Coron Artery Dis. 2013 Jun 7

    n= 210 pts with focal

    coronary lesions with mild

    luminal narrowing who

    received atorvastatin or

    pravastatin

    Fu with angiography &

    IVUS at 18 ms

    0

    0,2

    0,4

    0,6

    0,8

    1

    1,2

    Remodeling ratio

    1,071,03

    Baseline

    Follow-up

    Remodeling ratio (RR) : ratio of EEM area at

    the lesion to that at the proximal reference site.

  • 21

  • Shear stress

    shear stress,

    .

    Y Chatzizisis,,P Stone, Circulation. 2008;117:993-1002

    n=24 swine with

    induced diabetes &

    and fed a high-fat

    diet

  • 21

  • & shear stress( )

    010

    20

    30

    40

    Shear stress

    17,3

    22,18

    33,93

    Pretreatment

    Placebo

    Metoprolol

    .

    (dyne/cm2)

    C Liang et al., European Journal of Pharmacology 613 (2009) 7985

    n= 30male NZW

    rabbits on

    atherogenic diet

    p

  • Papaioannou TG, ..Stefanadis C, Artificial Organs Vol. 31, No. 8, 2007

    - stent

    stent.

    Stent

    stent

  • 21

  • Toutouzas K, Chatzizisis Y, Stefanadis C, 1st Department of Cardiology, University of Athens

    1st Cardiology Department, University of Thessaloniki/Harvard Medical School

    Shear Stress Map of the Reconstructed RCA

  • Injured Distal Aorta

    Non-Injured Proximal Aorta

    , ,

    . Porter TR et.al unpublished data

  • 21

  • .

  • .

  • . ,

    .

  • ,

    ,

  • Carl Sagan,