Intravascular Ultrasound and Near-infrared spectroscopy of - PowerPoint PPT Presentation

Intravascular Ultrasound and Near-infrared spectroscopy of non-culprit, non-steno7c segments for the predic7on of MACE Results from ATHEROREMO Rohit M. Oemrawsingh, MD MSc Op7cs in Cardiology, Zurich April 20th, 2018

Disclosures § Conflict of interest: NONE Netherlands Heart Founda6on, non-commercial charity à (grant no. NHS 2007B012 and NHS 2009B091 ) § Funding ATHEROREMO European Commission, Seventh Framework Programme à theme FP7-HEALTH-2007-2.4.2-1

PRESENTATION OUTLINE § (RF)IVUS and risk predic6on (n=581) § NIRS and risk predic6on (n=203 for 1 year FU, n=275 for 4 year FU)

ATHEROREMO European Collaborative Project on Inflammation and Vascular Wall Remodeling in Atherosclerosis

Background § ATHEROREMO à European collabora6ve research programme studying the rela6on of gene$c profile and novel circula$ng biomarkers with coronary plaque phenotype as determined by intravascular ultrasound and NIRS

Objec7ves § To assess the prognos'c value of coronary plaque detec6on, as evaluated with RF-IVUS and NIRS à adverse cardiovascular outcome § To inves6gate whether imaging of a single segment without significant luminal narrowing of a non-culprit coronary artery could be used for the purpose of risk stra6fica6on

Methods I § Prospec6ve, single-center, observa6onal study § With an indica6on, as determined by their trea'ng physician , for diagnos6c CAG and/or PCI § Real world se`ng of everyday clinical prac6ce, in which pa6ents with both stable angina and ACS present for coronary angiography. § Approved by the Medical Ethics Commiaee of the Erasmus MC and performed in accordance to the Declara6on of Helsinki. Wriaen informed consent was provided by all pa6ents.

Methods II § RF- IVUS and NIRS target segment of the non-culprit coronary artery of at least 40 mm in length and without significant luminal narrowing (< 50 % stenosis) as assessed by on-line angiography § Selec6on of the non-culprit vessels was predefined in the study protocol 1. Lee anterior descending artery 2. Right coronary artery 3. Lee circumflex artery

Methods III § Focus on predic6ng type 1 MI during FU, not on TLR events § In case of follow-up angiography, events were classified either as a definite culprit lesion-related (CLR) event (ISR or ST) or as related to a coronary site that was not treated during the index procedure (non-culprit lesion-related event) § In case angiographic informa6on on the endpoint related coronary site was not available ( e.g. in case of death), the event was classified as indeterminate

RF-IVUS European Collaborative Project on Inflammation and Vascular Wall Remodeling in Atherosclerosis

Results Patient characteristics (n=581) Age 61.6 years Men 75.6 % Diabetes 17.0 % Hypertension 51.6 % History of MI 31.7 % Indication for angiography: ACS 54.7 % Stable CAD 45.3 % Multi-vessel disease 39.6 % PCI performed 88.0 %

Results Imaged non-culprit coronary artery Left anterior descending 36.1 % Left circumflex 33.6 % Right coronary artery 30.3 % Median segment length 44.3 [33.8-55.4] mm

High-risk coronary lesions Virtual Histology- Lesion with plaque Lesion with minimal derived TCFA lesion burden ≥ 70% luminal area ≤ 4.0mm2

Results Imaged non-culprit coronary artery Left anterior descending 36.1 % Left circumflex 33.6 % Right coronary artery 30.3 % Median segment length 44.3 [33.8-55.4] mm Presence of high-risk lesions ≥ 1 VH-TCFA lesion 41.7 % ≥ 1 lesion with plaque burden ≥ 70% 21.3 % ≥ 1 minimal luminal area ≤ 4.0mm 2 31.3 %

Results 1-year MACE (definite culprit lesion-related events not counted) Death 17 Acute coronary syndrome 11 Unplanned coronary revascularization 17 MACE 45 Death or acute coronary syndrome 28

Results MACE P Presence of VH-TCFA HR 1.98 (1.09-3.60) 0.026 Lesion with plaque burden ≥ 70% HR 2.90 (1.60-5.25) <0.001 Lesion with minimal luminal area ≤ 4mm 2 HR 1.23 (0.67-2.26) 0.50

Results MACE P Presence of VH-TCFA HR 1.98 (1.09-3.60) 0.026 Lesion with plaque burden ≥ 70% HR 2.90 (1.60-5.25) <0.001 Lesion with minimal luminal area ≤ 4mm 2 HR 1.23 (0.67-2.26) 0.50 Death or ACS P Presence of Vh-TCFA HR 2.51 (1.15-5.49) 0.021 Lesion with plaque burden ≥ 70% HR 2.01 (0.92-4.39) 0.079 Lesion with minimal luminal area ≤ 4mm 2 HR 1.14 (0.53-2.49) 0.73

Results 25 23.1 Present Major adverse cardiac events (%) Absent 20.5 20 15.1 15 10.8 10 6.9 6.8 6.1 5.6 5 0 TCFA TCFA+MLA ≤ 4mm 2 TCFA+PB ≥ 70% TCFA+PB ≥ 70%+ MLA ≤ 4mm 2 Hazard ratio (95% CI) 1.96 (1.08-3.53) 2.26 (1.09-4.69) 3.47 (1.86-6.49) 3.70 (1.72-7.95) P value 0.024 0.025 <0.001 <0.001 Prevalence (%) 41.7 10.5 11.9 6.0

Results Presence of TCFA with PB ≥ 70% (large TCFA) Presence of TCFA with PB<70% (small TCFA) No TCFA 20 20 revascularization (%) 15 15 Death, ACS or 10 10 5 5 0 0 0 6 9 12 months 3 6 Large TCFA vs no TCFA p<0.001 Large TCFA vs no TCFA p=0.011 Small TCFA vs no TCFA p=0.033 Small TCFA vs no TCFA p=0.49

NIRS European Collaborative Project on Inflammation and Vascular Wall Remodeling in Atherosclerosis

Background § NIRS is based on diffuse reflectance spectroscopy § A FDA-approved NIRS system (InfraReDx) performs 1000 chemical measurements per 12.5 mm § Each measurement interrogates 1-2 mm 2 of vessel wall § Tissue scaaering and absorp6on of light in the NIR result in a wavelenght dependent return of light which can be displayed as an image map à chemogram § Cholesterol (monohydrate and ester) are both abundant in necro6c cores and has prominent molecular features in the NIR region

Chemograms as result of near-infrared spectroscopy

Gardner CM et al. JACC Cardiovasc Imaging. 2008; 1 :638–648

§ J Am Coll Cardiol. 2014 Dec 16;64(23):2510-8

Methods § NIRS target segment of the non-culprit coronary artery of at least 40 mm in length and without significant luminal narrowing (< 50 % stenosis) as assessed by on-line angiography § Primary endpoint à composite of all-cause mortality, non-fatal ACS, stroke and unplanned PCI during one-year follow-up, exclusive of events related to the culprit lesion at the index angiography § Secondary endpoints included 1) the composite of all-cause mortality and non-fatal ACS 2) the composite of all-cause mortality, non-fatal ACS and stroke 3) the composite of all-cause mortality, non-fatal ACS and unplanned PCI.

Baseline characteris7cs 203 April 16, 2009 – January 28, 2011

Baseline characteris7cs Age, years 63.4 ±10.9 Male, n (%) 148 (72.9) Diabetes Mellitus, n (%) 41 (20.2) Hypertension, n (%) 114 (56.2) Hypercholesterolemia, n (%) 115 (56.7) Smoking, n (%) 50 (24.6) Posi6ve family history, n (%) 120 (59.1) Previous MI, n (%) 79 (38.9) Previous PCI, n (%) 78 (38.4) Previous CABG, n (%) 6 (3.0) Previous stroke, n (%) 6 (3.0) Peripheral artery disease, n (%) 11 (5.4) History of renal insufficiency, n (%) 12 (5.9) History of heart failure, n(%) 9 (4.4)

Median total cholesterol (IQR) 4.20 (3.60-5.20) Median low-density lipoprotein (IQR) 2.47 (1.95-3.21) Median high-density lipoprotein (IQR) 1.14 (0.92-1.36) Median triglycerides (IQR) 1.26 (0.91-1.80) Sta6n, n (%) 181 (89.1) Indica'on for coronary angiography ACS, n (%) 95 (46.8) PCI / stent implanta6on, n (%) 179 (88.2) Extent of coronary artery disease No significant stenosis, n (%) 16 (7.9) 1-vessel disease, n (%) 106 (52.2) 2-vessel disease, n (%) 58 (28.6) 3-vessel disease, n (%) 23 (11.3)

Median LCBI 43 LCBI < Median LCBI ≥ Median P value N= 101 N=102 64.8 ±10.8 62.1 ±11.0 0.08 Age, years 67 (66.3) 81 (79.4) 0.041 Male, n (%) 15.0 (6.0-27.0) 88.5 (58.8-120.3) <0.001 Median LCBI History of hypercholesterolemia, stroke or PAD were iden6fied as predictors of con6nuous LCBI

Primary endpoint Adjusted HR: 4.04 95% CI: 1.3-12.3 P=0.01 SAP and ACS patients (p-value for heterogeneity=0.14)

Secondary endpoint: All-cause mortality and non-fatal ACS Adjusted HR: 8.91 95% CI: 1.1-72.3 P=0.04

Secondary endpoint: All-cause mortality, non-fatal ACS and stroke Adjusted HR: 10.59 95% CI: 1.4-83.3 P=0.03

Secondary endpoint: All-cause mortality, non- fatal ACS, unplanned PCI Adjusted HR: 3.56 95% CI: 1.1-11.2 P=0.03

No. of patients AR IBIS-3 581 Baseline IVUS-VH 389 192 Baseline NIRS 128 45 in both studies 275 pa6ents available for analysis

Baseline characteristics Atheroremo IBIS-3 median Age, year 63.3 60.2 Man 72% 84% Diabetes 21% 21% Smoker 24% 29% Statin user 89% 95% Indication: STEMI 13% 12% NSTEMI 33% 27% SAP 54% 61% Multiple vessel disease 48% 42%

Distribution LCBI region of interest 40 N=275

Distribution LCBI max 4mm 227 N=275

Conclusion § IVUS plaque characteris6cs and LCBI in a non-steno'c target segment of a non-culprit vessel reflect larger coronary vulnerability § No claims on sensi'vity or specificity given the number of events § Key ques6on remains: NPV or PPV? § Neither on temporal plaque stability