Despite a well-developed understanding of the pathophysiology of MI and sudden cardiac death, more than 1 million people in the United States die each year from these disorders. Post-mortem findings have revealed that the majority of these events are caused by rupture of a vulnerable atherosclerotic plaque—typically a large lipid-core plaque (LCP)—leading to occlusive thrombosis.

The disadvantage of relying on autopsy findings, of course, is that the cause of the fatal coronary event is identified too late, after the opportunity to provide preventive treatment has already passed. Is it possible to identify LCPs prone to rupture and thrombosis in vivo, before a serious coronary event has occurred?

In a recent paper published in JACC: Cardiovascular Interventions, Ryan D. Madder, MD, from Spectrum Health in Grand Rapids, Michigan, and colleagues evaluated the role of intracoronary near-infrared spectroscopy (NIRS) in finding culprit STEMI-causing plaques. NIRS has been developed to identify LCP in patients undergoing coronary angiography, demonstrating that culprit lesions in stable patients with angina frequently contain LCP. Perhaps, the authors hypothesized, combining NIRS results with intravascular ultrasound (IVUS) imaging results would provide sufficient information to define a signature of vulnerable plaques—and, hence, targets for preventive therapy.

"Unlike the thrombus in STEMI, which occurs in close proximity to the onset of symptoms, the lipid is likely to have been present in the arterial wall well before STEMI onset," Dr. Madder explained in an interview with CardioSource WorldNews. "It may, therefore, be amenable to detection prior to the event."

Accuracy of the Novel NIRS Catheter System

Dr. Madder and his team recruited 20 consecutive STEMI patients who were referred for primary PCI at the Frederik Meijer Heart & Vascular Institute. The STEMI culprit lesions in these patients were evaluated with NIRS-IVUS imaging (TVC Imaging System; Infraredx; Burlington, MA) after restoration of arterial flow, but before alteration of the plaque by stenting, and compared to non-culprit segments of the patients' vessels. Madder et al. also compared STEMI culprit segment findings to autopsy specimens selected for their LCP findings, with the hypothesis that current NIRS-IVUS findings would be similar to NIRS findings in autopsy specimens with very large LCP by histology.

In 19 of the 20 STEMI patients, a specific signature of LCP was identified at the culprit lesion (one patient had a calcified nodule). After imaging was completed, stents were placed in all but one patient, who was referred for bypass surgery. Lipid core burden index (LCBI), the primary measure of interest in this study, was calculated as the fraction of pixels indicating lipid within a region multiplied by 1,000; each 10 mm culprit and non-culprit segment was scanned for the maximum LCBI in any 4 mm region (maxLCBI_4mm).

Compared with non-culprit segments in the same vessel, maxLCBI_4mm was 5.8-fold higher in culprit segments. This relationship was confirmed by comparison of autopsy specimens: maxLCBI_4mm was 87-fold higher than histology-negative specimens.

NIRS Signature of Culprit Lesions

What should interventional cardiologists look for when performing NIRS-IVUS in patients with acute STEMI? According to these study results, a threshold of maxLCBI_4mm >400 distinguished STEMI culprits from histology-negative autopsy specimens, with high rates of accuracy (sensitivity = 85%; specificity = 98%).

Vulnerable plaques were visually distinct from non-culprit segments. "The lipid core at the culprit site is often circumferential in nature and sometimes quite narrow—features captured by the maxLCBI_4mm measure," Dr. Madder said. "The NIRS signature is characterized by a large lipid core, which often wraps around the circumference of the artery at the culprit site."

In general, STEMI culprit segments had greater plaque and more frequent calcification than did non-culprit segments in both the culprit artery and histology-negative autopsy specimens. Although plaque burden, LCBI, and calcification were all successful in differentiating culprit from non-culprit segments on univariable analysis, only maxLCBI_4mm (as determined by NIRS-IVUS) emerged as a significant predictor in multivariable analysis.

Next Steps

Although the current study had a small cohort of only 20 consecutive patients, these novel in vivo findings do provide support for the role of NIRS in detecting a signature of plaques prone to rupture and thrombosis. "Most importantly for predictive and preventive purposes," the study authors wrote, "it is possible that the large LCPs observed at STEMI culprit sites were present and detectable before thrombus formation and the acute coronary event."

"Although there are no immediate clinical implications of these findings, this NIRS signature is likely to undergo formal testing in future studies to determine if the signature can provide site-specific identification of future coronary events," Dr. Madder answered when asked about plans for a future study. "A larger multicenter study is currently underway to validate the findings of the initial study, and is being performed at Spectrum Health, and with David Erlinge, MD, at Lund University in Lund, Sweden." Hopefully, the authors concluded, further investigation of the NIRS signature will confirm its efficacy in predicting vulnerable plaques, facilitating the development of more effective preventive therapies.

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Madder RD, Goldstein JA, Madden SP, et al. JACC Cardiovasc Interv. 2013 July 12. [Epub ahead of print]

Keywords: Spectroscopy, Near-Infrared, Plaque, Atherosclerotic, Thrombosis, Autopsy, Stents

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