Hybrid Imaging Approach Offers High Discriminatory Ability for Vulnerable Coronary Plaques

Compared with histology alone, a hybrid method of invasive imaging that combines virtual-histology intravascular ultrasound (VH-IVUS) and OCT may be better than either modality alone at correctly identifying advanced atherosclerotic coronary plaques, according to a study published online October 1, 2015, ahead of print in Circulation: Cardiovascular Imaging. 

“Our results should assist clinicians and researchers in planning future studies to identify high-risk plaques in vivo,” write study author Martin R. Bennett, MD, PhD, of the University of Cambridge (Cambridge, England), and colleagues.

The researchers looked at coronary arteries harvested from 14 human hearts (age range 47-85 years; 71.4% male). Causes of death in donors were both cardiovascular (n = 8) and noncardiovascular (n = 6).

In all, 258 regions of interest were identified and assessed by histology for tissue composition and plaque classification. These findings were then compared with those of OCT alone, VH-IVUS alone, and combinations of features from VH-IVUS and OCT to create a “hybrid” imaging modality.

Reliable Alone, Better Together

Of the 73 regions of interest classified as fibroatheroma on histology, 22 met the criteria for thin-cap fibroatheroma (TCFA). All were imaged by both VH-IVUS and OCT.

On VH-IVUS, plaque area, fibrous tissue, dense calcium, and necrotic core areas were increased in TCFA compared with other fibroatheroma, although plaque burden was similar.

On OCT, both maximum lipid arc value and minimal fibrous cap thickness were similar in TCFA and other fibroatheroma, but the median number of continuous frames with fibrous cap thickness < 85 µm was higher in TCFA (6.5 vs 2.0; P = .03).  

Using existing criteria, VH-IVUS showed sensitivity of 63.6% and specificity 78.1% for TCFA identification compared with 72.7% and 79.8%, respectively, on OCT. Additionally, diagnostic accuracy was marginally better with OCT (79.0% vs 76.5%). The maximum lipid arc measured via OCT showed a strong ability to discriminate fibroatheroma (area under the curve [AUC] 0.92; 95% CI 0.87-0.97) and TCFA (AUC 0.86; 95% CI 0.81-0.92), with a maximum lipid arc of ≥ 80 degrees found to be the optimal cut-off value.

On hybrid imaging, combining plaque burden ≥ 50% and a maximum lipid arc of ≥ 80 degrees increased sensitivity and diagnostic accuracy to 86.4% and 80.5%, respectively, for TCFA identification. Incorporating VH-defined fibroatheroma further increased the accuracy to 85.0%. However, the highest diagnostic accuracy (89.0%) was seen when VH-defined fibroatheroma was combined with fibrous cap thickness < 85 µm for 3 continuous frames.

“Our data highlight that both VH-IVUS and OCT can reliably identify fibroatheroma based on existing methods, with diagnostic accuracies exceeding 77.5%,” the study authors write. “Sensitivities were also reassuringly high (> 70.1%), indicating that both modalities can readily identify large accumulations of [necrotic core/lipid].”

But Dr. Bennett and colleagues observe that some false-positive results were seen with both modalities, “suggesting that TCFA may be overestimated in vivo” and that future efforts should be made to reduce these mistakes going forward.

Unrealistic and Expensive

Importantly, the authors say, 64.2% of all fibroatheroma had minimal fibrous cap thickness < 85 µm at some location within the plaque, suggestion that “any single-frame measurement of [fibrous cap thickness] on OCT is unlikely to represent overall cap thickness.”

But in an editorial accompanying the study, Gary S. Mintz, MD, of the Cardiovascular Research Foundation (New York, NY), says that with positive and negative predictive values of 26.4% and 94.6% for identification of TCFA with VH-IVUS, respectively, and 30.8% and 95.9% with OCT, respectively, “by themselves, both techniques were fundamentally flawed.”

The suggestion that the combination of imaging modalities is better than either alone attempts to use the “strengths of each technology to compensate for the weaknesses of the other,” Dr. Mintz contends. But doing so is not necessarily the answer, he says.

Using 2 catheters and 2 machines “is clinically cumbersome, unrealistic, and expensive, and it requires some method to co-register the 2 techniques,” Dr. Mintz notes, adding that the 3 currently available IVUS technologies “are not interchangeable, and each, alone or in combination with OCT, requires validation.” Other issues include intellectual property rights that may limit commercialization of certain combinations and the risk that combining component technologies may sacrifice the quality of each for the sake of convenience and expediency.

“Although histopathologic correlations are important, imaging findings that reliably predict (or exclude) events are even more important than studies showing that one or another technology (or any combination of technologies) correlate better with histopathology,” Dr. Mintz says. “This is true even if the imaging technology is flawed when compared with histopathology; clinical data trumps histopathologic correlations, but it takes more time and resources.”

Note: Dr. Mintz is the editor-in-chief of TCTMD, which is owned and operated by the Cardiovascular Research Foundation.

Sources:  
1. Brown AJ, Obaid DR, Costopoulos C, et al. Direct comparison of virtual-histology intravascular ultrasound and optical coherence tomography imaging for identification of thin-cap fibroatheroma. Circ Cardiovasc Imaging. 2015;8:e003487.
2. Mintz GS. Optical coherence tomography and virtual-histology intravascular ultrasound: strange bedfellows? … or not? [editorial]. Circ Cardiovasc Imaging. 2015;8:e004045. 

Disclosures:

• The study was funded by grants from the British Heart Foundation, the BHF Cambridge Centre for Research Excellence, the Cambridge National Institute of Health Research Biomedical Research Centre, and Heart Research UK. 
• Dr. Bennett reports no relevant conflicts of interest. 
• Dr. Mintz reports serving as a consultant for and receiving honoraria from ACIST, Boston Scientific, Infraredx, St. Jude, and Volcano; and that his employer receives fellowship or research support from Boston Scientific, Infraredx, St. Jude, and Volcano.  

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