Catheter-Based Measurement of Plaque Lipid Predicts Future Events

A high lipid burden in nonculprit vessel plaque as assessed by catheter-based near-infrared spectroscopy (NIRS) substantially increases the likelihood of future ischemic events, according to a study published in the December 16, 2014, issue of the Journal of the American College of Cardiology.

Ryan D. Madder, MD, of Spectrum Health (Grand Rapids, MI), told TCTMD in a telephone interview that the technology, though still being optimized, appears useful in identifying not just at-risk plaque but also the “vulnerable patient” more broadly at risk of future events.

Investigators led by Eric Boersma, PhD, MSc, of Erasmus Medical Center (Rotterdam, the Netherlands), looked at 203 patients referred for diagnostic angiography and, if Take Home Message 12.8.2014necessary, PCI due to stable angina or ACS at their institution and enrolled in the NIRS substudy of the larger ATHEROREMO-IVUS study between April 2009 and January 2011. All underwent catheter-based NIRS (InfraReDx; Burlington, MA) in a single nonculprit artery with less than 50% stenosis.

Mean age was 63.4 years, almost three-quarters (72.9%) were men, and almost half (46.8%) presented with ACS. PCI was performed in 88.2% during the index angiography.

The median lipid core burden index (LCBI) of the nonculprit vessels, as assessed by NIRS, was 43.0 (IQR 15.0-90.0). Regression analyses showed higher LCBI values in men and patients with hypercholesterolemia, stroke, or PAD. There was no difference in LCBI between those who presented with stable angina vs ACS.

Higher Lipid Burden Quadruples Risk

Over 1-year MACCE (all-cause mortality, nonfatal ACS, stroke, or unplanned revascularization) not attributable to the culprit vessel—the primary endpoint—occurred in 10.4% of patients, with unplanned revascularization (all via PCI) the most frequent event at 5.9%. On regression analysis, only LCBI, a history of stroke, and PAD were associated with the primary endpoint.

The rate of nonculprit lesion–related MACCE was fourfold higher in patients with an LCBI value at or greater than the median vs those with a value below. Other composite endpoints were also higher in the group with a higher lipid burden (table 1).

Table 1. One-Year Outcomes (Excluding Culprit Lesion–Related Events)

The association between a higher LCBI and occurrence of the primary endpoint remained after adjustment for multiple clinical characteristics (adjusted HR 4.04; 95% CI 1.33-12.29), as did those of all secondary endpoints. However, mortality did not differ for those above vs below median LCBI. In addition, there was no interaction between stable compared with ACS presentation and LCBI’s predictive effect, although the researchers note that this analysis may have been underpowered.

Analysis of all events, including those related to the culprit lesion, also showed an increased 1-year incidence of the primary endpoint for patients with higher rather than lower LCBI values (19.6% vs 7.9%; P = .015).

The authors acknowledge several limitations. Not only was the sample size small but the study was performed at a single center and thus requires independent validation. Moreover, the median LCBI should not be considered a threshold for prognosis, they caution; larger sample sizes are needed to determine cut-off values that provide optimal sensitivity and specificity.

Factors Mitigating Prognostic Power of NIRS

In an accompanying editorial, Sanjay Kaul, MD, MPH, of Cedars-Sinai Medical Center (Los Angeles, CA), and Jagat Narula, MD, PhD, of the Icahn School of Medicine at Mount Sinai (New York, NY), offer several possible explanations for what they call the “rather modest prognostic utility” of NIRS seen in the study:

  • The LCBI threshold was based on the median for this study cohort, and much higher cut-offs in other studies have yielded mixed results for prognostic utility
  • Inflammatory cell infiltrate—a hallmark of vulnerable plaque—cannot be detected by NIRS
  • Nearly one-third of acute events are linked to unruptured plaque
  • Future culprit lesions located in other vessels or distal to evaluated segments were inaccessible to NIRS
  • Aggressive secondary prevention may have mitigated the risk of plaque rupture, resulting in too few hard events
  • The editorialists also point to the omission of any discussion of whether LCBI offered incremental prognostic utility beyond the clinical variables of history of stroke and PAD that were associated with MACCE.

Identifying the ‘Vulnerable Patient’

“There are 2 principal applications of intracoronary imaging devices to predict the risk of future events,” Dr. Madder said. One aims at identifying plaque with high-risk features and then tracking whether such characteristics cause future site-specific events, while the other “uses intracoronary imaging to identify a ‘vulnerable patient’ at increased risk for future cardiovascular events in general.” This study focuses on latter, he indicated.

Dr. Madder said it has been known for decades that the concentration of lipids in the blood predicts a patient’s risk of future cardiovascular events. However, it is not the lipid in the blood but rather the lipid in the arterial tissue that causes events. “Now with this NIRS catheter we finally have a tool that can reliably identify lipid in the tissue, so perhaps it shouldn’t be surprising that it actually predicts events,” he noted.

“The big question that still looms is whether this information can be used to improve patient care,” he added, “and right now we still don’t know.”

Each imaging modality provides a unique set of data, but each also has its own limitations, Dr. Madder observed. He endorsed the editorialists’ suggestion that combining imaging strategies including IVUS to detect plaque burden, OCT to assess fibrous cap thickness and NIRS to measure plaque composition “with systemic markers of inflammation, might improve prognostic and predictive utility making this approach more clinically useful.”

Integrating these capabilities into a single catheter may be “more of an engineering problem than anything else,” Dr. Madder said, adding that “the closest thing we have now is a combined NIRS and IVUS catheter [TVC Imaging System; InfraReDx].”

Meanwhile, NIRS itself carries some practical advantages, he noted, such as the ability to provide straightforward, quantitative measurement of lipid burden that bypasses the need for qualitative interpretation of imaging signals, and to evaluate an entire artery quickly in real time.

The combination of NIRS and IVUS is being used in the ongoing PROSPECT II trial, which is looking at the feasibility of plaque passivation or “sealing,” and the Lipid-Rich Plaque study, he said. “A lot of individuals including myself are anxiously awaiting the results. There is hope that the combined NIRS-IVUS device can identify not only the vulnerable patient but also perhaps the vulnerable plaque.”


Sources:
1. Oemrawsingh RM, Cheng JM, García-García HM, et al. Near-infrared spectroscopy predicts cardiovascular outcome in patients with coronary artery disease. J Am Coll Cardiol. 2014; 64:2510-2518.

2. Kaul S, Narula J. In search of the vulnerable plaque: is there any light at the end of the catheter [editorial]? J Am Coll Cardiol. 2014;64:2519-2524.

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Disclosures
  • Dr. Boersma reports serving as a consultant to Medtronic, Sanofi, and Servier.
  • Dr. Kaul reports no relevant conflicts of interest.
  • Dr. Narula reports receiving grant support from GE and Philips Healthcare.
  • Dr. Madder reports receiving research support from InfraReDx.

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