A Beautiful View

The latest intravascular imaging modalities help avoid unnecessary stenting and optimize PCI outcomes.

Intravascular diagnostic imaging provides important information in evaluating the need for a coronary stent and, after implantation, in ensuring optimal stent apposition and minimizing restenosis. Newer approaches to imaging are designed to provide more nuanced information than traditional X-ray angiography and to overcome some of angiography’s limitations.

“There are two fundamental decisions you have to make when doing a stenting procedure,” said Cardiology Today’s Intervention Editorial Board member Gary S. Mintz, MD. “The first is, do you stent that patient or lesion, or not? And the second is, what’s the best way to stent — how do you optimize it to get the best possible results?”

Currently, the main modalities used or being investigated to assess lesions for stent implantation are fractional flow reserve, optical coherence tomography, IVUS, FFR computed tomography (FFR-CT) and near-infrared spectroscopy (NIRS). These technologies offer data about lesion characteristics, both pre-intervention and post-stent deployment. Each modality has shown distinct advantages, but the scope and quality of the available research varies — as does interventionalist opinion.

“The researchers in the IVUS field did a very nice job on establishing findings that were predictive of stent thrombosis and restenosis, and at least collecting data comparing IVUS and angiography,” said Mintz, who is chief medical officer of the Cardiovascular Research Foundation, New York. “The researchers in the OCT field haven’t done that legwork, and that is very disappointing.”

FFR and FAME II

In determining whether a lesion is significant enough to warrant stent implantation — particularly in non-left main lesions — there does appear to be a clear gold standard, according to experts interviewed: FFR.

“Data in non-left main lesions overwhelmingly favor the use of FFR to decide whether a lesion is significant or not,” Mintz said. “The data about left main lesions are very balanced, and you can make the case for either FFR or IVUS.”

Data from the FAME II trial found that FFR-guided PCI plus optimal medical therapy (OMT) reduced the need for revascularization in patients with stable CAD compared with medical therapy alone.

“FFR is, by far, the technique which has been most thoroughly and scientifically validated,” said Bernard De Bruyne, MD, PhD, lead author of FAME II with the Cardiovascular Center Aalst, Belgium.

De Bruyne said FAME II showed that hemodynamically significant stenoses (FFR ≤0.80) should be considered for revascularization, regardless of their angiographic appearance.

“FAME II has demonstrated that hemodynamically significant stenoses should be revascularized by drug-eluting stents,” De Bruyne said. “Many other trials and registries had shown that hemodynamically insignificant stenoses (FFR >0.80) do not benefit from revascularization; thus, theoretically, all lesions with questionable stenoses should be ‘FFR’ed.’”

Mintz said FAME II established some valuable criteria for stent implantation and delineated the situations in which OMT is inadequate.

“FAME II asked the question, ‘If you have a lesion with an FFR <0.80, is OMT enough?’ And the study indicated that the answer is no,” he said. “If you compare those lesions with OMT vs. OMT plus stent implantation, the stent implantation group does better, and the medical therapy alone group does worse.”

There are also data supporting the cost-effectiveness of FFR-guided stenting. A cost-effectiveness substudy of FAME II, presented at the 2012 Transcatheter Cardiovascular Therapeutics Scientific Symposium, found that FFR-guided PCI is cost-effective “in terms of quality-adjusted life years” compared with medical therapy.

“FFR has the best outcome and cost data,” said Morton J. Kern, MD, professor of medicine at the University of California, Irvine, and Cardiology Today’s Intervention Editorial Board member. “There really is none for the others.”

Inside IVUS Imaging

IVUS is an imaging modality that allows imaging of a lesion from inside the artery. It is considered useful in assessing lesion characteristics in the preliminary phases of stent placement, according to Kern.

“Many operators choose to perform IVUS imaging in the preliminary phases of stent placement,” he said. “That tool is used to assess both the lesion characteristics, such as calcium or fibrous tissue or maybe thrombus, and the size of the reference vessel of both the lumen and the external elastic lamina. Basically, the entire vessel dimensions.”

Mintz said in terms of optimizing stent placement, there is a wealth of data supporting IVUS-guided PCI. He cited a meta-analysis of published, peer-reviewed randomized studies comparing IVUS guidance with angiography in the placement of bare-metal stents.

“The meta-analysis of those seven trials indicates that IVUS-guided bare-metal stent implantation reduces restenosis, repeat revascularization and major adverse events, but not death or MI,” he said. “Those studies, in general, did not report stent thrombosis.”

A different meta-analysis, which included one randomized trial and 10 observational studies involving 19,619 patients, showed that compared with angiography guidance, IVUS-guided DES implantation was associated with a reduced incidence of death (P<.001), MACE (P=.008) and stent thrombosis (P<.001). The incidence of MI, and target lesion and target vessel revascularization was similar between both arms.

Recently, 1-year results of the ADAPT-DES trial, which were presented at TCT 2012, indicated that IVUS guidance results in a significantly reduced incidence of stent thrombosis and MI. The multicenter study, which was the largest prospective registry of IVUS use to date, evaluated 8,576 consecutive PCIs with DES at 11 centers. The study was designed to establish the frequency, timing and correlates of early and late stent thrombosis. IVUS was used in 3,343 of these patients.

“It was an IVUS vs. non-IVUS comparison, with about 3,300 patients in the IVUS group and about 5,000 in an angiography-guided group,” Mintz said. “In that comparison, IVUS guidance was associated with a 50% reduction in stent thrombosis and MI.”

IVUS provides image resolution of about 150 mcm compared with 10 mcm offered with OCT. Kern said IVUS is likely to evolve toward utilizing high frequency transducers that achieve resolution of about 50 mcm.

“IVUS imaging has two kinds of technical catheters, one is a mechanically rotating core, and the other is an electronically rotated series of transducers on the catheter that create an electronic image. Both provide the same information with the same detail,” he said. “The future of IVUS is high-definition ultrasound imaging to improve resolution from 150 mcm down to 50 mcm, roughly.”

Other interventionalists said the superior spatial resolution offered by OCT might indicate that IVUS will become obsolete.

“IVUS has been around for 20 years and — let’s face it — was never able to show any clinically relevant usefulness,” De Bruyne said. “Maybe in some small niches; but IVUS is on its way out.”

OCT: High Resolution, Limited Penetration

Another important imaging modality in lesion assessment is OCT. This approach provides high-resolution images of a lesion’s surface characteristics, but is limited in its ability to penetrate into the vessel wall.

According to Kern, “OCT can tell us more about the surface characteristics [compared with IVUS], but not much about the entire external elastic lamina because it doesn’t have enough depth of penetration.”

OCT provides clear information about strut apposition after a stent is implanted, Kern said.

“If we use OCT post-stent implantation, we can see the struts very well,” he said. “We can see more detail than we would like to, in fact, because it shows us small amounts of thrombus on the stent or dissection flap that we never would have seen with IVUS or with angiography.”

The use of OCT in stent implantation is still in its early stages, and interventionalists are not yet certain of its long-term role.

“OCT has a much better spatial resolution than IVUS, but the risk is that it will follow the same fate [as IVUS],” De Bruyne said. “Yet, OCT is currently being tested in a more scientifically meaningful way than IVUS. Thus, who knows what OCT will become?”

Mintz said he doesn’t consider the existing data on OCT to be thorough or definitive.

“There was only one small OCT vs. angiographic study that was published,” Mintz said. “The three Italian center study showed that OCT reduced event rates compared with angiography.”

In the study of 670 PCI patients, which was published in EuroIntervention, angiographic guidance alone was compared with angiographic guidance plus OCT for PCI. The study was conducted at three high OCT-volume facilities in Italy and found that OCT detected adverse features needing further intervention in 34.7% of cases. At 1 year, the patients in the OCT group had significantly lower rates of cardiac death (1.2% vs. 4.5%; P=.01) and the study’s primary endpoint of cardiac death or MI (6.6% vs. 13%; P=.006).

Mintz also cited a study conducted in Toyohashi, Japan, and published in the journal Circulation: Cardiovascular Interventions. In this study of 70 patients, 35 were randomly assigned to undergo stent implantation using Frequency Domain (FD) OCT alone, with final stent expansion assessed by IVUS. In the remaining 35 patients, IVUS guidance was used for stent implantation, with final apposition assessed by FD-OCT. The researchers determined that there were “no differences regarding the procedural, fluoroscopy time and contrast volume” between the two modalities. Additionally, the study found that although clinical success rates were similar, the visibility of the vessel border was significantly lower in the OCT group (P<.05). OCT guidance was associated with smaller minimum and mean stent expansion and more frequent significant residual reference stenosis compared with IVUS.

“The study didn’t have a clinical endpoint; the endpoints were acute stent dimensions and plaque burden at the stent edges,” Mintz said. “The conclusion was that IVUS guidance was better than OCT guidance in that small number of patients with only acute imaging endpoints.”

Mintz said although OCT for intravascular imaging may be in its infancy, the technology itself has been in existence for many years. Considering this, he said, the amount of clinical data available has been “trivial.”

“There has been very little work establishing OCT criteria for stent guidance, OCT criteria for stent optimization or OCT criteria for stent sizing,” he said. “Then we have this one study from Italy that suggests it can improve patient outcomes, but there’s been so little work done to support that.”

De Bruyne said OCT has been useful in yielding valuable information about late stent thrombosis, but added that having imparted this lesson, OCT may render itself unnecessary. He cited an editorial by William Wijns, MD, which ruminates on the long-term usefulness of an outgrown research tool.

“The risk is that once we have learned the lesson, we won’t need OCT anymore,” he said. “It’s like the ‘first-grade teacher’ phenomenon: The teacher is indispensable in learning to read and write, but once you know it, you don’t need the teacher anymore.”

According to Ik-Kyung Jang, MD, PhD, director, Cardiology Laboratory for Integrative Physiology and Imaging, Massachusetts General Hospital, OCT ultimately will need to be substantiated by further proof of its efficacy.

“We should prove that OCT will indeed improve patient outcomes,” he said. “Otherwise, the expense cannot be justified.”

Mintz said although OCT is touted as having potential, this potential is of limited value in the absence of supporting data.

“You can summarize almost every talk on OCT as saying ‘OCT has promise to do this, that, and the other thing.’ But we need data,” he said.

Emerging Modalities

Other approaches to intravascular imaging are thought to have potential, but are not yet widely used. NIRS is a technology that emits near-infrared light into the lesion tissue and identifies lesion characteristics based on the pattern of light absorption into the tissue.

“NIRS is a good research tool with no demonstrated clinical value yet,” Kern said.

Jang said he and colleagues have not found NIRS to be a useful approach.

“NIRS does not add anything,” he said.

Mintz said NIRS might prove valuable for its ability to assess the characteristics of plaque.

“NIRS is a promising technique that detects lipid-rich plaques and, therefore, may be able to predict their consequences,” he said.

In Asia, cardiologists are using intravascular angioscopy, a technology that is no longer available in the United States, Kern said.

“This requires balloon occlusion of the vessel and replacement of the blood with saline, allowing the doctor to look directly at the tissue and stent surfaces,” he said. “But it doesn’t help much in telling whether the struts are apposed or not apposed to the wall, so it’s not used routinely, and it’s not used in the United States at all for clinical purposes.”

However, a potential paradigm shift in lesion assessment could come in the form of an investigational technology that evaluates FFR using computed tomography: FFR-CT. Results from the DeFACTO study suggest promise for this modality, as it showed that noninvasive measurement of FFR helps to accurately identify which lesions must be assessed invasively. Currently in development by HeartFlow, this approach builds on the FFR concept through an interface that analyzes CT scans, allowing FFR calculation through a Web-based service, according to the HeartFlow website.

The 17-center DeFACTO study evaluated 252 stable patients with suspected CAD. All patients were evaluated using CT, invasive angiography, invasive FFR and then FFR-CT.

The study found that FFR-CT was superior to CT alone in identifying flow-restricting lesions. Per-patient sensitivity and specificity of FFR-CT was also higher than that of CT alone using an area-under-the-curve analysis.

The diagnostic accuracy of FFR-CT was 73%, which did not meet the study’s primary endpoint.

“The study showed that in an unselected patient population, FFR-CT is not yet ready,” De Bruyne said. “Yet, it also showed that FFR-CT improves the accuracy of CT, and provided FFR-CT makes some progress, FFR-CT will prevail above all other noninvasive tests. This might become a real paradigm shift.”

Mintz said although there is a great deal of mathematical and physical background work that has been done on FFR-CT, he is not convinced by the strength of the data.

“The clinical data have been extremely disappointing,” he said. “[FFR-CT]’s been touted as improving on CT for the diagnosis of coronary disease and is considered a way of suggesting whether the stenoses are significant or not; but compared with FFR, which is now the gold standard, the results are very disappointing. I look at the data and think, ‘OK, you guys have a lot of work to do.’”

The Future of Intravascular Imaging

With the current data on intravascular imaging not compelling enough to prompt a clinician consensus, interventionalists are not entirely sure which of these modalities — if any — will ultimately prevail as the standard of care.

“The future depends on data that show these technologies improve patient care and outcome,” Jang said. “Even with IVUS, there are no convincing data.”

One thing that seems clear, according to Kern, is that FFR will likely remain at the forefront of lesion evaluation.

“The short answer is that FFR will remain the best tool for physiologic lesion assessment,” he said. “I expect OCT to rise in use for strut apposition and continue as a tool for research of vulnerable plaque.”

Jang said there is currently a 3,000-patient registry of OCT under way, which is being led by researchers at the Massachusetts General Hospital. Currently, 2,000 patients have been enrolled and are being followed.

However, according to Mintz, until the findings with OCT are as significant as those reported for IVUS, “IVUS will continue to be the technique of choice in optimizing stent implantation.” – by Jennifer Byrne

Disclosure: De Bruyne has received institutional research grants from Abbott, Biotronic, BSCI, Medtronic, St. Jude Medical, and has served as a consultant for St. Jude Medical. Jang receives research grants from and has consulting agreements with InfraReDx and St. Jude Medical. Kern is a consultant for St. Jude Medical and Volcano Therapeutics. Mintz is a consultant for St. Jude Medical and is a consultant for and has received grant support from Boston Scientific and Volcano Therapeutics. The Cardiovascular Research Foundation is a partner of SLACK Incorporated, publisher of Cardiology Today’s Intervention.