Update and current status on PROSPECT II/PROSPECT ABSORB Optics in - - PowerPoint PPT Presentation

Update and current status on PROSPECT II/PROSPECT ABSORB

Optics in Cardiology Zurich 2018

Prof David Erlinge

Dept of Cardiology Lund University Lund, Sweden

Non-Flow Limiting Vulnerable Plaque

• A plaque that is non-flow limiting, but will cause a

coronary event.

• FFR/iFR can by definition not detect Non-flow

limiting plaques.

• We need other methods to detect these plaques

Lipid in Plaque

Thin Cap Fibroatheroma with rupture (70%) Lipid core in all Erosion (no obvious rupture (30%) Lipid pool in both (about 50% have lipid pool (M Joner personal communication) Calcified nodule (2-5%). No lipid.

Approximately 85% of plaques causing sudden death have lipid core or lipid pool

Falk et al., EHJ 2013

Lund-Stockholm outcome study

Improvements

• Both 20 and 50 MHz ultrasound giving

“OCT-like” resolution combined with depth

• 4 x faster pullback
• Thin cap detection with collagen

algorithm

NIRS technology: Intravascular Diffuse Reflectance

5

Vessel Wall Specular Reflections

Diffuse Reflectance detected

NIRS Light Uncollected light

• The returned near infrared light

along with knowledge of the delivered light allow computation of absorption spectra

• Absorption spectra can be used to

identify molecules

Absorbance Spectra

NIRS generated Chemogram

maxLCBI4mm: 0-1000

Erlinge, (review) J Internal Medicine 2015

NIRS-IVUS in pathology specimens

(NIRS)-IVUS detects plaque volume

• Intravascular ultrasound

(IVUS) can see External Elastic Lamina (EEL) and Lumen.

• EELarea-Lumenarea/EELarea=

Plaque Burden PB/Percent Atheroma Volume (PAV)

Plaque burden/ volume Lumen Lumen EEL

McPherson JA et al. JACC Img 2012;5:S76–85; Stone, GW et al., NEJM, 2011. The prospective importance of plaque burden has been confirmed in the PREDICTION and VIVA trials: Stone,P Circ 2012, Calvert JACC CVI 2011

Median 3.4 yr MACE rate per lesion (%)

0,0% 0,6% 0,5% 2,5% 9,5%

0% 2% 4% 6% 8% 10% 12% <40% 40% - 50% (n=904) 50% - 60% (n=1,239) 60% - 70% (n=798) ≥70% (n=298)

Plaque burden

thousands

PROSPECT: Correlates of Non-culprit Lesion Related Events: Impact of plaque burden

31% of pts having at least one non-culprit lesions with PB≥70% But only 28 of these 298 >70% plaques caused a coronary event NNT = 11

Plaque burden >70% Lumen

Lipid rich plaques defined by NIRS cause STEMI

Typical circular lipid-rich plaque with MaxLCBI4mm of 920 in LAD in a patient with an inferior STEMI.

Erlinge, (review) J Internal Medicine 2015

Core lab confirmation of a NIRS treshold for STEMI plaques

Confirmation that MaxLCBI4mm >400 is detected in the majority of STEMI culprit plaques

Madder…Erlinge, ATVB 2016

A cut-off of maxLCBI >400 had high sensitivity and specificity to detect a culprit NSTEMI plaque

NSTEMI and Unstable angina culprit plaques have more lipid as detected with NIRS

Madder…Erlinge, Catheterization Cardiovascular Interventions, 2014

NIRS and Plaque Burden

Khan… Madder, abstract TCT 2015 Rarity of Non-culprit PB70 Lesions with Concurrent Large Lipid Burden

Whereas PB70 lesions accounted for 12.0% of all non-culprit plaques, PB70 lesions with a concurrent maxLCBI4mm ≥400 are rare, accounting for only 2.1% of all non-culprit lesions.

NIRS added to Plaque Burden

Khan… Madder, abstract TCT 2015

Two Lesions Having a Large Plaque Burden

This figure highlights the ability of combined NIRS-IVUS imaging to differentiate lesions having a large PB into those with (left) and without (right) substantial lipid content.

Post-thrombectomy

LCBI: 604 LCBI: 466 Thrombus and Lipid-rich Aspirate

Reduced lipidcore in NIRS.

Pre-thrombectomy In vivo histological validation of NIRS detecting lipid rich plaque

Erlinge et al, EHJ CV imaging 2014

Pre-thrombectomy Post-Thrombectomy

200 400 600 800

LCBI

p = 0.0001

Pre-thrombectomy Post-Thrombectomy

200 400 600 800 1000

maxLCBI4mm

p = 0.001

Thrombectomy is Coronary Liposuction

Erlinge et al, EHJ CV imaging 2014

NIRS in non-culprit plaquespredicts clinical

• utcomes
• Pooled Atheroremo-NIRS and

IBIS-3 – Serruys

• Large single-center registry

with extended FU – Madder

• ORACLE-NIRS – Brilakis
• Sweden-NIRS - Erlinge

Schuurman et al., EHJ 2017 Danek et al., CV Revasc Med 2017 Karlsson…Erlinge, submitted

• LCBI and maxLCBI in non-culprit segments strongly predicts MACE

Madder et al, EHJ CVI 2016

Prospective Identification by NIRS of a Lipid- Rich Plaque that Caused a Myocardial Infarction

Site of Index MI –was stented Possible Vulnerable Plaque in LAD

4 Months New MI

New culprit lesion at lipid-rich site.

• High lipid in D1 (first

culprit) and in prox LAD.

• maxLCBI4mm: 722 in D1,

573 in LAD

NIRS: Lipid rich, collagen low plaque predicted NSTEMI and ruptured plaque

Lipid detection algorithm (yellow) Collagen detection algorithm (red) (only measured in lipidrich areas) LAD ruptured plaque 4 months later

White areas indicating thin cap (low collagen) in LAD plaque

PROSPECT II Study

900 pts with ACS at 16 hospitals

NSTEMI or STEMI >12h IVUS + NIRS (blinded) pre-PCI in culprit vessel(s) Successful PCI of all intended lesions (by angio ± FFR/iFR)

Formally enrolled

IVUS + NIRS (blinded) (prox 6-10 cm of each coronary artery)

3-vessel imaging post PCI

Angiography to core lab: Adjudication to non-culprit or culprit lesion. IVUS + NIRS if possible

Coronary Event

PI: David Erlinge Chairman: Gregg Stone Enrollment complete dec 2017: 902 patients

• Primary endpoint: Patient level non-culprit lesion-related major adverse

cardiac events (NC-MACE) through 2 years: cardiac death, MI, unstable angina/progressive angina requiring repeat hospitalization or symptom- driven revascularization by CABG or PCI, adjudicated to an originally untreated non-culprit lesion.

PROSPECT II (Natural History Study): PRIMARY ENDPOINT

PROSPECT II Study

PROSPECT ABSORB RCT

900 pts with ACS after successful PCI

3 vessel IVUS + NIRS (blinded)

≥1 IVUS non-flow limiting lesion with ≥70% plaque burden?

Routine angio/3V IVUS-NIRS FU at 2 years

Yes

(N=182)

No

(n=720) ABSORB BVS + GDMT (N~100) GDMT

(N~100)

R 1:1

Clinical FU for ≥2 years (up to 15 years in registers)

PROSPECT ABSORB, The ABSORB BVS

Neo-media vascular smooth muscle cells

Cap sealing

PROSPECT ABSORB PRIMARY ENDPOINT

• The minimal luminal area (MLA) at the randomized

non-culprit lesion site in patients treated with the ABSORB BVS + GDMT compared to GDMT only measured at 25 months (superiority)

• Death, TV-MI, TLR (noninferiority, not powered)

MLA

MLA

2 years ”Plaque Sealing”

Follow up in P2/PA

• 95% 2y follow up in PROSPECT2
• 87% angiographic follow up at 25 month in

PROSPECT ABSORB

ABSORB II: 3 year data

• Depressing results

Serruys et al, Lancet 2016

SAFETY PROSPECT ABSORB

• In PROSPECT ABSORB we have not seen any

definite stent thrombosis

• Some minor complications: Occluded side branch,

distal dissection, one restenosis upon reexamination.

• Most PROSPECT ABSORB patients in Lund look

great at reexamination

• DSMB (Serruys, Koenig, Tijssen and

Wykrzykowska) recommended the study to continue at the last DSMB meeting. However, they recommended PSP technique and DAPT for 2 years.

• 25 months follow up completed dec 2019