Imaging coronary lesions with near-infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS) can show which plaques are vulnerable to future cardiovascular events, which may inform how, or whether, these plaques should be treated in the future.
That was a takeaway message from a focused session titled “Detection of a Vulnerable Plaque” held Saturday during Week 7 of CRT 2021 Virtual.
David Erlinge, MD, PhD, of Lund University, Sweden, explained that NIRS is an imaging modality approved by the U.S. Food and Drug Administration to identify and quantify lipid-rich plaque in human coronary arteries. Retrospective reports and a recent prospective study suggest that lipid-rich plaques detected by intracoronary NIRS imaging are associated with adverse outcomes.
NIRS data generate chemograms whereby the lipid-rich plaques appear as yellow areas, signifying a high probability of lipid, surrounded by red areas, which signify low probabilities of lipid. The Lipid Core Burden Index (LCBI) is the fraction of pixels with the probability of lipid divided by all analyzable pixels within the region of interest, multiplied by 1,000. The maximum LCBI within any 4-mm segment of a lesion, known as the maxLCBI4mm, represents the segment with the highest percentage of lipid-rich plaques. For example, a maxLCBI4mm of 625 means that 62.5% of the pixels in the measured 4-mm segment of a lesion have a high probability of being lipids.
The Lipid Rich Plaque (LRP) study, published in 2019 in The Lancet, showed that maxLCBI4mm >400 was a strong predictor of major adverse cardiovascular events (MACE) at both the patient and segment levels in patients with suspected coronary artery disease. The PROSPECT II study, published March 13 in The Lancet, showed similar results but with a maxLCBI4mm >324.7.
Gregg W. Stone, MD, of the Icahn School of Medicine at Mount Sinai and the Cardiovascular Research Foundation, discussed lessons from PROSPECT ABSORB, a randomized trial that was nested within the PROSPECT II randomized trial.
PROSPECT ABSORB, which was published in the Journal of the American College of Cardiology in November 2020, randomized 182 PROSPECT II patients to treatment with the Absorb bioresorbable vascular scaffold (Abbott) with guideline-directed medical therapy (GDMT) or GDMT alone. This study found that treatment of angiographically mild non–flow-limiting lesions with large plaque burden, small lumen areas and high lipid content was safe and substantially enlarged luminal dimensions during follow-up as compared to GDMT alone.
Stone explained that thin-cap fibroatheroma (TCFA) is the precursor lesion of most plaque ruptures. The TCFA, he said, has a well-formed necrotic core consisting of cholesterol, cholesterol esters, dead lymphocytes and macrophages, and other necrotic debris. This is separated from the lumen by a thin, metabolically active fibrous cap infiltrated by macrophages. When this ruptures, it releases the prothrombotic material it had contained, which may lead to an ST-elevation myocardial infarction, total occlusion, nonocclusive thrombus or small thrombus. Stone compared the TCFA to a volcano that erupts when enough pressure has mounted from within.
Stone said the lessons from the PROSPECT I, PROSPECT II and LRP studies are that the most powerful predictors of future cardiovascular events arising from untreated non-flow-limiting lesions are large plaque burden and high lipid content, i.e., fibroatheromas.
What is the right treatment course?
He gave the example of a 65-year-old man, a prior smoker, whom Stone said was a Fortune 500 CEO, who presented with exertional dyspnea, hypertension, hypercholesterolemia treated by atorvastatin, and a stress echocardiogram that showed 1-mm exertional ST-depression but normal resting and stress left ventricular ejection fraction.
Even though the ISCHEMIA trial would indicate conservative treatment, Stone said, the operator decided to catheterize the patient, and the angiogram showed lesions with 20% stenosis in the proximal and mid left anterior descending artery. Fractional flow reserve was measured at 0.88, which again would not be an indication for percutaneous coronary intervention. The operator performed NIRS-IVUS imaging of the two lesions, which both showed high plaque burden (>70%) and high lipid content (maxLCBI4mm = 568 and 361).
Stone asked the CRT audience whether these lesions should be revascularized.
“I think today the answer has to be no, but tomorrow, maybe,” he said.
When CRT 2021 Virtual Course Chairman Ron Waksman, MD, of MedStar Washington Hospital Center, pressed Stone about whether he feels pressure to treat such lesions, Stone responded, “I definitely do.”
“Can I tell you today that you should treat those lesions?” Stone said. “No I can’t.”
Instead of performing PCI, Stone said that if presented with such a patient, he would probably prescribe a PCSK9 inhibitor with the goal of lowering the patient’s low-density lipoprotein cholesterol.
Takashi Akasaka, MD, PhD, of Wakayama Medical University, Japan, presented data showing that NIRS-IVUS imaging can differentiate among plaque rupture, plaque erosion and calcified nodules by more accurately evaluating plaque cavity, convex calcium and maxLCBI4mm as compared with optical coherence tomography.
Waksman was principal investigator of the LRP study, which was funded by Infraredx. Erlinge and Stone were co-principal investigators of PROSPECT II, which was funded by Abbott Vascular, Infraredx and The Medicines Company.
CRT 2021 Virtual takes place Fridays and Saturdays through April 24. On-demand content from the meeting is available here. The conference will take a break April 3, which is Easter weekend.