It’s Both the Vulnerable Patient and the Vulnerable Plaque James Muller MD Brigham and Women’s Hospital CRT 19 February 2017

Disclosure Statement of Financial Interest No Disclosures

Cardiology Clinic Schedule Two Patients, Both Destined to Have a Coronary Event in the Next 2 Years 1:00 PM Joseph Smith MRN:43758417 Dx: Vulnerable Patient 1:20 PM Ellen Jones MRN:98249712 Dx: Vulnerable Patient due to Vulnerable Plaque

Vulnerable Patient Detection for Primary Prevention is Difficult

Is this a Vulnerable Patient? 60 year old female with atypical chest pain – April, 2008 Past Medical History: hypertension, obesity No family history of CAD No history of smoking Medications: metoprolol, nifedipine,triamterene Physical Exam: normal except for obesity Courtesy Dr. Ryan Madder, Beaumont Hospital

Coronary Artery Calcium Score = 0 April 2008 Coronary Artery Calcium Score = 0 Courtesy Dr. Ryan Madder, Beaumont Hospital

March, 2008 CT Angiogram Interpretation: No Significant Coronary Disease Courtesy Dr. Ryan Madder Beaumont Hospital

In March, 2009, 11 months after CTA Patient calls EMS due to sudden onset chest pain radiating to left arm. Courtesy Dr. Ryan Madder, Beaumont Hospital

Coronary Angiography Courtesy Dr. Ryan Madder, Beaumont Hospital

Courtesy Dr. Ryan Madder, Beaumont Hospital

Will it be Possible to Detect and Treat a Vulnerable Coronary Plaque and Prevent a Coronary Event? For Primary or Secondary Prevention? Courtesy Dr. Ryan Madder, Beaumont Hospital

Vulnerable Patient Detection for Secondary Prevention is Less Difficult – The Role of Invasive Imaging

Invasive NIRS Catheter Detection of Coronary Lipid-rich Plaques – Autopsy Comparison 40 mm 36 mm 20 mm 26 mm

Invasive Detection of LCBI in Non-culprit Artery Identifies Vulnerable Patients Above the Median Median LCBI = 43 Courtesy Drs. Rohit Oemrawsingh and Patrick Serruys, ESC, 2013

In the cohort of 70 post PCI patients, only 4 had maxLCBI4mm >600 Vulnerable Plaque? Unstable Angina at 7 months New culprit at vulnerable plaque site Stent placed in STEMI culprit In the cohort of 70 post PCI patients, only 4 had maxLCBI4mm >600 in non-stented area. Courtesy of Dr. Ryan Madder Spectrum Hospital Grand Rapids, MI Confidential

VP, 1989

Critics of Vulnerable Plaque Detection Efforts After 28 years of searching, the vulnerable plaque field is doomed – you are wasting your time and our money.

The Vulnerable Plaque Hype-pothesis Steve Nissen, MD, CRT Meeting, 2010 Requiem for the ‘vulnerable plaque’ Peter Libby and Gerard Pasterkamp, EHJ, March 2015 The Myth of the “Vulnerable Plaque” Transitioning From a Focus on Individual Lesions to Atherosclerotic Disease Burden for Coronary Artery Disease Risk Assessment Armin Arbab-Zadeh, MD, PHD,* Valentin Fuster, MD, PHD: JACC 2015

The Lipid-rich Plaque (LRP) Study Dr. Ron Waksman, PI PI, Europe, Dr The Lipid-rich Plaque (LRP) Study Dr. Ron Waksman, PI PI, Europe, Dr. Carlo Di Mario 2 year MACE from a new lesion at vulnerable patient and vulnerable plaque level 1,562 patients with ACS or SA underwent NIRS-IVUS imaging of 2 or more Vessels during PCI

LRP Study Vulnerable Plaque Endpoint Cause of Second Event Relationship between Max 4 mm LCBI and new culprit lesion in a given 30 mm segment of proximal, mid, or distal artery Max 4 mm LCBI 500 Suspected vulnerable plaque Cause of First Event Confidential 20

PROSPECT 2 Study PROSPECT / ABSORB RCT 900 ACS Patients Undergoing PCI Drs. Stone, Erlinge, Co-PIs Dr. Serruys, Chair, DSMB 900 ACS Patients Undergoing PCI “PROSPECT 2” 600 Patients “ABSORB” 300 pts > 70% Plaque Burden,Non-Flow -Limiting BVS Scaffold BVS Scaffold + GDMT 150 Patients GDMT Only 150 Patients NIRS/IVUS Predicts MACE LCP No LCP LCP No LCP Assess Treatment Effect in Sub-set with LCP

PROSPECT 2 – 900 Patients imaged and followed for events PIs –Dr. David Erlinge and Dr. Gregg Stone PROSPECT ABSORB -- 300 patients with PB>70% randomized to scaffold or standard care - Secondary endpoint - Safety and efficacy of BVS in lesions with large plaque burden which are LRP+ vs LRP-

Soon, the Data will Speak So when those results are available, you will no longer have to listen to Steve and me howling away -- Soon, the data will speak Soon, the Data will Speak