F Prati

San Giovanni H. and CLI Foundation, Rome

Le espressioni della placca che

preoccupano il clinico: progressione o

vulnerabilità?

Euro Image Research

CardioLUCCA

Marzo 2017

Che cosa preoccupa il cardiologo clinico?

• Presenza di aterosclerosi • Vulnerabilità di placca/paziente • Progressione di malattia

First of all look carefully at the coronary angiogram ………….Absence of significant narrowing does not mean much !

Male 65 Years. Anterior NSTEMI with mild increase in Troponin and T wave inversion

Mild vesssel irregularities = Atherosclerosis

Male 63 Years Effort and rest chest pain. Angina?

Marked vessel irregularities = Advanced stage atherosclerosis

Female 81 Years NSTEMI triggered by high blood pressure

Smooth vessels = No Atherosclerosis

Date of download: 5/12/2016 Copyright © The American College of Cardiology. All rights reserved.

From: CORONARY ARTERY CALCIUM SCORE IS SUPERIOR TO CAROTID PLAQUE SCORE FOR PREDICTING

CARDIOVASCULAR DISEASE EVENTS: THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS

J Am Coll Cardiol. 2016;67(13_S):1557-1557. doi:10.1016/S0735-1097(16)31558-3

At baseline, the 4955 participants were mean (standard deviation) 61.6 (10.1) years old and 52.8% female; 48.9% had

CAC and 50.8% had at least one carotid plaque. After 11.3 (3.0) years of follow-up, 709 CVD, 498 CHD, and 262

stroke/TIA events occurred. The CAC score was a stronger predictor of CVD and CHD and had better reclassification

statistics than carotid plaque score, except for stroke/TIA (Table).

A zero coronary artery calcium score

Hecht et al JACC 2010

Che cosa preoccupa il cardiologo clinico?

• Presenza di aterosclerosi • Vulnerabilità di placca/paziente • Progressione di malattia

What is the best way to detect atheroscerosis ?

• Should we rely on extension of CAD: 1,2 or 3 vessel

disease? • Should we rely on presence of peripheral

atherosclerosis ? • Should we try something new ?

• i.e. Assessment of the exact amount of plaque volume at CT scan for primary prevention

• i.e Assessment of plaque composition with IC imaging for secondary prevention

Why IC Imaging?

• Large plaque burden • Large lipid pool • Thin fibrous cap • Small lumen area • Inflammation

Features of plaque vulnerability

IVUS NIRS-IVUS OCT

High Res. 15 µ Small Penetration

Res. 150 µ Identif. of lipid components

Res. 150 µ Good penetration

The concept of plaque vulnerability

HRP was defined as plaque with PR (RI >1.1) and/or LAP ( > 30 HU).

Plaque Characterization by Coronary Computed Tomography Angiography and the Likelihood of Acute Coronary Events in Mid-Term Follow-Up Motoyama S et al. JACC 2015

Plaque characterisation by CTA

Motoyama S, et al. J Am Coll Cardiol 2015;66:337–46. CTA, computed tomography angiography; HRP, high-risk plaque;

LAP, low attenuation plaque; PR, positive remodelling; SS, significant stenosis.

HRP was defined as plaque with PR (RI >1.1) and/or LAP (>30 HU)

Histopathologic Characteristics of Atherosclerotic Coronary Disease

and Implications of the Findings for the Invasive and Noninvasive Detection of Vulnerable Plaques

Narula et al JACC 2013

Histopathologic Characteristics of Atherosclerotic Coronary Disease

and Implications of the Findings for the Invasive and Noninvasive Detection of Vulnerable Plaques

Narula et al JACC 2013

Local inflammation

Di Vito L, Agozzino M, Marco V, Ricciardi A, Concardi M, Romagnoli E, Gatto L,

Calogero G, Tavazzi L, Arbustini E, Prati F. Identification and quantification of

macrophages presence in aterosclerotic plaques by OCT. Eur Heart J Cardiovasc

Imaging. 2015;16:807-813

Male, 58 y/o 14thJuly 2014: inferolateral STEMI treated with a DES in the RCA 17thJuly 2014: PCI OCT-NIRS-IVUS study of non culprit lesion in LCx

NIRS-IVUS OCT

New trials

Catania,Ferratto

Siracusa Umberto I

Messina. G Martino

Roma S Giovanni Roma Pol Gemelli

Bologna Sant’Orsola

Milano, Monzino

Cotignola GVM Care and Research

Grosseto. Misericordia

Isernia. Veneziale

Siena. Sant’Anna

Caltanisetta, Sant’Elia

Brotzu Cagkiari

Madrid S. Carlos

Warsav Military Hosp.

N 700 pts

OCT vulnerable plaque criteria

Lesion presenting all of the

following four features:

• TCFA <65 μm

• Lipid pool arc >180º

• MLA <4.0 mm2

• Macrophages

Clinical outcome

Composite of cardiac death and/or target vessel MI (STEMI/NSTEMI)

F Prati et al. LP, lipid pool.

LP arc

>180º

MLA

<4 mm2, TCFA

<70 µm

Macrophages

ClinicalTrials.Gov

Distal

Prox

Mixed plaque with

irregular surface

Lipid pool Thin FC

Lipid pool Thin FC

Small LA

LP Plaque with

irregular surface

Lipid pool

REF

The pt died 4 years

after The OCT

study

Che cosa preoccupa il cardiologo clinico?

• Presenza di aterosclerosi • Vulnerabilità di placca/paziente • Progressione di malattia

EEMCSA is the external elastic membrane cross-sectional area ,

LUMENCSA is the luminal cross-sectional area.

PAV Reduct. 1%

Change in percent atheroma volume (PAV) = PAV (end of treatment) − PAV (baseline).

Improvement of lipid

profile

Regression of atherosclerosis

Clinical benefit

PROVE-IT N Engl J Med 2004

20

21

22

23

24

25

26

27

Primary end-point

Pravastatin 40

mgAtorvastatin

80 mg

20

21

22

23

24

25

26

27

Primary end-point

Pravastatin 40

mgAtorvastatin

80 mg

Euroimage Research

How to identify lesions that

progress vs vulnerable lesions

I doubt it can be done

Kolodgie et al. Heart 2004

Ruptured and healed plaques are

more severely narrowed

G Souteyrand1, P Motreff1, L Di Vito2, V Marco2, N Amabile3, A Chisari2, T Kodama4, L

Tavazzi5, Jagat Narula6, F Crea , E Arbustini4, F Prati2

Post intervention

and FU assessment

Eurointervention 2014

EROSION

The healing process after rupture

often leads to plaque progression

…..yet 88.2% of patients with similar plaques did not have a major adverse cardiovascular event in a nonculprit lesion during 3.4 years of follow-up.

Attilio Maseri, Enrico Ammirati, Francesco Prati

Corerspondence N Engl J Med 2011

• In many ACS studies it is difficult to

distinguish events related to plaque

rupture/erosion from those caused by plaque

progression

• Soft end-point are included like

hospitalization due to angina that may be

due to plaque progression

Take Home Message – Identification of atherosclerosis is key for primary

prevention

– Recent studies showed that it is rationale to identify pts at higher risk of coronary event and put them on a more agrresive anti-thrombotic therapy

– Imaging modalities (CT for primary prevention) and IC imaging modalities (OCT for secondary prevention) potentially better identify patients with a more aggressive atherosclerosis

– Pheraps in the next future IC imaging will be used to identify vulnerable plaques to be treated with stenting or vulnerable patients to be treated with a more aggressive drug treatment.

– Plaque progression is related to a worse clinical outcome and can be caused by plaque healing after rupture

Madder et al. JACC Int 2013

• S. L. • Male, 64 years old • Cardiovascular Risk factors

– Hypertension – Family History of CAD – Previous Smoking Habit

• 12th August 2014: infero-postero-lateral STEMI treated with primary PCI and DES of LCX

• 18th August 2014: PCI OCT-NIRS-IVUS guidance of non culprit lesion (Distal Right Coronary Artery)

Clinical Case OCT vs NIRS

ACS. Non culprit RCA lesion

LP?

Inflammatory cells?

Calcium

YES

Inflammatory Cells + LP FC Thick 0,07 mm

Ulceration NON Ulceration

OCT to address the mechanism of ACS

Calcific Nodule No TCFA

Take Home Messages

– IVUS, NIRS-IVUS and OCT have recently offered new insights on the composition of vulnerable plaques

– Large superficial plaques with local inflammation and clacific nodules are features related to plaque vulnerabilty

– Pheraps in the next future IC imaging will be used to identify vulnerable plaques to be treated with stenting or vulnerable patients to be treated with a more aggressive drug treatment.

Clinical Case OCT vs NIRS 2 • S. L.

• Male, 64 years old

• Cardiovascular Risk factors – Hypertension

– Family History of CAD

– Previous Smoking Habit

• 12th August 2014: infero-postero-lateral STEMI treated with primary PCI and DES of LCX

• 18th August 2014: PCI OCT-NIRS-IVUS guided of non culprit lesion (Distal Right Coronary Artery)