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 Erosion (no obvious rupture (30%) with rupture (70%) Lipid pool in both (about 50% have lipid pool (M Joner Lipid core in all 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 • 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 NIRS Specular Light Reflections Diffuse Reflectance detected Vessel Wall Absorbance Spectra Uncollected light 5
NIRS generated Chemogram maxLCBI 4mm : 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. • EEL area -Lumen area /EEL area = Plaque Burden PB/Percent Atheroma Volume (PAV) EEL Lumen Plaque burden/ Lumen volume
PROSPECT: Correlates of Non-culprit Lesion Related Events: Impact of plaque burden 12% 31% of pts having at least one non-culprit Median 3.4 yr MACE rate 9,5% lesions with PB≥70% 10% per lesion (%) 8% But only 28 of these 298 >70% plaques caused a coronary event 6% NNT = 11 4% 2,5% 2% 0,6% 0,5% 0,0% 0% ≥70% <40% 40% - 50% 50% - 60% 60% - 70% (n=904) (n=1,239) (n=798) (n=298) thousands Plaque burden Plaque Lumen burden McPherson JA et al. JACC Img 2012;5:S76 – 85; Stone, GW et al., NEJM, 2011. >70% The prospective importance of plaque burden has been confirmed in the PREDICTION and VIVA trials: Stone,P Circ 2012, Calvert JACC CVI 2011
Lipid rich plaques defined by NIRS cause STEMI Typical circular lipid-rich plaque with MaxLCBI 4mm 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 MaxLCBI 4mm >400 is detected in the majority of STEMI culprit plaques Madder…Erlinge, ATVB 2016
NSTEMI and Unstable angina culprit plaques have more lipid as detected with NIRS A cut-off of maxLCBI >400 had high sensitivity and specificity to detect a culprit NSTEMI plaque Madder …Erlinge, Catheterization Cardiovascular Interventions, 2014
NIRS and Plaque Burden 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. Khan… Madder, abstract TCT 2015
NIRS added to Plaque Burden 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. Khan… Madder, abstract TCT 2015
In vivo histological validation of NIRS detecting lipid rich plaque Pre-thrombectomy LCBI: 604 Thrombus and Lipid-rich Aspirate Post-thrombectomy LCBI: 466 Reduced lipidcore in NIRS. Erlinge et al, EHJ CV imaging 2014
Thrombectomy is Coronary Liposuction 800 1000 p = 0.001 800 600 p = 0.0001 maxLCBI 4mm 600 LCBI 400 400 200 200 0 0 Pre-thrombectomy Post-Thrombectomy Pre-thrombectomy Post-Thrombectomy Erlinge et al, EHJ CV imaging 2014
NIRS in non-culprit plaquespredicts clinical outcomes • Pooled Atheroremo-NIRS and IBIS-3 – Serruys Schuurman et al., EHJ 2017 • Large single-center registry Madder et al, EHJ CVI 2016 with extended FU – Madder • ORACLE-NIRS – Brilakis Danek et al., CV Revasc Med 2017 • Sweden-NIRS - Erlinge Karlsson … Erlinge, submitted • LCBI and maxLCBI in non-culprit segments strongly predicts MACE
Prospective Identification by NIRS of a Lipid- Rich Plaque that Caused a Myocardial Infarction Possible Vulnerable Site of Index Plaque in LAD MI – was stented 4 Months New MI New culprit lesion at lipid-rich site.
NIRS: Lipid rich, collagen low plaque predicted NSTEMI and ruptured plaque • High lipid in D1 (first culprit) and in prox LAD. • maxLCBI 4mm : 722 in D1, 573 in LAD White areas indicating thin cap (low collagen) in LAD plaque Lipid detection Collagen detection algorithm (yellow) algorithm (red) (only measured in lipidrich areas) LAD ruptured plaque 4 months later
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) PI: David Erlinge Formally enrolled Chairman: Gregg Stone 3-vessel imaging post PCI IVUS + NIRS (blinded) (prox 6-10 cm of each coronary artery) Coronary Event Angiography to core lab: Adjudication to non-culprit or culprit lesion. IVUS + NIRS if possible Enrollment complete dec 2017: 902 patients
PROSPECT II (Natural History Study): PRIMARY ENDPOINT • 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 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? Yes No (N=182) (n=720) R 1:1 ABSORB BVS GDMT (N~100) + GDMT (N~100) Routine angio/3V IVUS-NIRS FU at 2 years Clinical FU for ≥2 years (up to 15 years in registers)
PROSPECT ABSORB, The ABSORB BVS Cap sealing Neo-media vascular smooth muscle cells
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) 2 years MLA MLA ”Plaque Sealing ” • Death, TV-MI, TLR (noninferiority, not powered)
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
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