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IVUS for the Interventional Cardiologist: The Current State-of-Play
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Although initially described in the early 1970s, technological advancements during the past 2 decades have allowed IVUS to evolve into an over-the-wire, high-resolution cross-sectional in vivo imaging modality, now available in most well-equipped cardiac cath labs worldwide. In addition to its widespread utilization in clinical trials that quantify the serial change in coronary atheroma burden as a means of assessing mechanistic efficacy of novel treatment approaches, IVUS has proven itself as an invaluable adjunctive imaging tool for contemporary interventional cardiology practice.
Assessment of Lesion Severity
Intravascular ultrasonography enables the precise quantification of plaque and lumen dimensions, lesion morphology and the true distribution of plaque prior to anticipated PCI. In particular, when PCI is planned, the use of IVUS has been traditionally preferred over functional studies when the anatomic distribution (eg, involvement of ostium or bifurcation) or lesion morphology (eg, ulceration vs. calcification as the cause of angiographic haziness) is crucial for decision-making.
Intravascular ultrasonography is often utilized for assessing the significance of lesions that appear ambiguous on angiography. However, within the epicardial (non-left main) coronary tree, the accuracy of specific IVUS cutoff values has not been extensively validated in a prospective fashion with stress myocardial perfusion imaging, or with myocardial fractional flow reserve. Prospective clinical outcomes data for corresponding IVUS and FFR cutoff values have only been evaluated in small retrospective studies. Accordingly, there remains ongoing debate regarding the optimal IVUS-based cutoff that corresponds to an FFR-based ischemic threshold for epicardial lesions. Prior studies have suggested that an IVUS-derived minimum lumen area (MLA) of 4 mm2 is appropriate for clinical decision-making of whether to revascularize, as well as for the delivery of favorable clinical outcomes.
Panels A and B show the angiographic projections of what seems to be an ostial stenosis of the left main coronary artery (LMCA), despite intracoronary nitroglycerine administration and a patent mammary graft. However, Panels C (ostial LMCA) and D (distal LMCA) show no significant atherosclerosis and significantly smaller ostial lumen area by IVUS. Minimum lumen area by IVUS at the left main ostium was 11.4 mm2 compared with 24.2 mm2 at the distal left main region.
Source: Puri R. J Am Coll Cardiol Cardiovasc Interv. 2012;7:697-707; reprinted with permission.
Although yet to be prospectively evaluated with clinical outcomes, further attempts at correlating lesion severity on IVUS with FFR (as the “gold-standard” for assessing hemodynamic significance) have identified optimal cutoff values on IVUS to predict an FFR of <0.80 as being an MLA of <2.4 mm2, although with modest specificity. Variation in the optimal cutoff MLA were also noted according to the spatial location of the coronary lesion (<2.4 mm2 for the left anterior descending and right coronary arteries; <1.6 mm2 for the left circumflex coronary artery). A similar study showed better correlation in larger vessels, with an optimal cutoff MLA of <2.7 mm2 in lesions with reference vessel diameters of 3 mm to 3.5 mm (receiver operator area under curve, 0.77). It is likely that a variety of other factors such as lesion length, volumetric plaque burden and the interplay between the coronary microvasculature and upstream conduit segments will deliver more meaningful information regarding the physiological significance of epicardial stenoses.
Intravascular ultrasonography has played a pivotal role in assessing the significance of left main coronary arterial lesions, which are notoriously difficult to accurately assess with angiography alone. The larger size and limited variability of left main length has led to a greater degree of concordance between IVUS and FFR measurements. An IVUS-derived MLA of 5.9 mm2 and minimum lumen diameter (MLD) of 2.8 mm were found to most accurately correlate with a FFR of <0.75 across the left main coronary lesion. These cutoff values were prospectively applied to patients with angiographically ambiguous left main coronary stenoses, whereby patients with an FFR of <0.75 across a left main lesion underwent revascularization, and those with FFR of ≥0.75 remained medically treated. The 38-month rate of survival between these two groups was identical.
Although yet to be prospectively evaluated with clinical outcomes, a similar analyses of left main coronary lesions of 30% to 80% diameter stenosis severity has identified an IVUS-derived MLA of <4.8 mm2 as being predictive of an FFR of <0.80. Despite the use of prior conservative IVUS-derived MLA cutoffs to guide decision-making for ambiguous left main lesions, the latest evidence would suggest that using an MLA cutoff of <6 mm2 is safe to guide a left main coronary stenosis revascularization strategy, with a 2-year event-free survival rate of 98% in those who were conservatively managed compared with 95% in those undergoing revascularization (P=NS). The results of the study provide further support for the utility of IVUS alone in guiding an appropriate treatment strategy for patients with angiographically indeterminate, unprotected left main stenoses.
IVUS-Guided PCI: Is There a Benefit?
Despite suggestive evidence to the contrary, there is still a general consensus within the interventional cardiology community that IVUS-guided stent implantation has a limited role in routine daily practice for demonstrating clinical benefit. This has been largely a result of ambiguous results from prior small, underpowered, randomized trials and observational registries within the bare-metal stent era. In addition, the current lack of validated, universal criteria for achieving optimal stent deployment across a range of lesion subsets has made it difficult for interventional cardiologists to embrace the concept of IVUS-guided PCI. Furthermore, increases in procedural time and issues pertaining to training and reimbursement have meant that in North America, the general rate of IVUS use has struggled to climb beyond 10% of all coronary interventions performed.
The use of IVUS to optimize lesion dilatation was first proven to be beneficial during the plain old balloon angioplasty (POBA) era, whereby significant increases in MLD were obtained following IVUS-guided POBA, without increases in complication rates. Following this, IVUS-guided POBA was found to result in a clinically significant reduction in target lesion revascularization rates at 2 years. In the era of BMS deployment, a seminal study with IVUS-guided BMS implantation highlighted the opportunity of replacing an anticoagulation regimen for a dual antiplatelet-only regimen following stent insertion optimized with IVUS-guidance.
Similar to these results, a separate trial confirmed significantly lower 9-month TLR following IVUS-guided BMS implantation. Although the first randomized trial failed to show statistical significance in the clinical benefit of IVUS-guided BMS implantation vs. an angiographic-guided approach, there were trends toward showing benefit despite the study being underpowered with low numbers of enrollment.
Although differences in 6-month TLR rates were low, subgroup analysis from another large trial did, however, show a 12-month benefit of IVUS-guided BMS implantation in vessels of 2.5 mm to 3.5 mm diameter, with accompanying significant benefits observed during saphenous vein graft intervention. The two randomized trials that followed showed conflicting results, with one trial showing no significant improvement in 6- and 12-month MACE rates, whereas the other trial showed significant improvements in 6- and 12-month clinically driven TLR, as well as a significant reduction in the rate of death and MI.
The advent of drug-eluting stents, however, with accompanying observations of remarkably low rates of in-stent restenosis perhaps contributed to the stifling of the emerging enthusiasm to undertake IVUS-guided PCI, despite IVUS proving crucial for determining the mechanisms implicated in stent thrombosis and restenosis involving the use of DES. Although no randomized trials have been performed to assess the utility of IVUS-guided stenting in the DES era, registry data suggests that IVUS-guided DES implantation is associated with significantly reduced stent thrombosis rates and the need for repeat revascularization, including superior 30-day and 2-year rates of death and MI, with benefit also observed during complex bifurcation stenting. As modern day interventional cardiologists tackle more complex lesions with PCI, earlier lessons from the DES era have taught us the critical importance of appropriate stent deployment, which is often better facilitated with IVUS.
IVUS and Left Main Lesions
Currently, there are no systematic randomized data suggesting the benefit of an IVUS-guided approach for left main PCI. The lack of a systematic randomized trial has meant that the current level of evidence exists from retrospective analysis of registry data coupled with expert opinion. The most comprehensive level of evidence in favor of an IVUS-guided approach for left main PCI stems from a post-hoc analysis of the MAIN-COMPARE registry. Acknowledging the various limitations of this analysis that involved propensity score matching, the investigators reported a significantly lower cumulative mortality rate within the IVUS-guided unprotected left main PCI group receiving a DES compared with the angiography-alone group that underwent stenting.
Although it is unlikely that a randomized clinical trial specifically evaluating the efficacy of an IVUS-guided approach for left main PCI will occur, the eagerly anticipated results of the EXCEL trial will help to further ascertain the utility of IVUS-guided PCI for unprotected left main coronary lesions.
From a procedural standpoint, however, IVUS plays a pivotal role in assessing plaque shift, especially following PCI of distal/bifurcation left main lesions, and is also critical for the optimization of post-procedural MLA following PCI to reduce restenosis rates. In the context of left main bifurcation stenting with DES, the final post-intervention MLA at the ostium of the circumflex branch was the only significant predictor of restenosis. For those patients who underwent a single crossover stent strategy, a post-intervention ostial circumflex MLA of ≥4 mm2 was associated with a restenosis rate of 6% compared with 50% in those whose ostial circumflex MLA was ≤4 mm2 (P=.04). Similarly in those who received two stents, a post-intervention ostial circumflex MLA of ≥5.5 mm2 was associated with a restenosis rate of 15% compared with 67% in those whose ostial circumflex MLA was ≤5.5 mm2 (P=.03). Despite the lack of any published data for describing the optimal post-procedural MLA of the left main coronary main-branch, expert consensus would recommend post-dilating the main branch to more than 8.5 mm2 to reduce the rate of TLR, and aiming for an MLA of more than 5.5 mm2 for the ostia of each daughter branch.
The “Sepal” wire technique for aorto-ostial left main coronary artery (LMCA) stenting in a patient who presented with syncope and was found to have extrinsic LMCA compression by the pulmonary artery (PA). Panel A: An additional workhorse coronary guidewire seated within the aortic (Ao) cusp (Sepal wire), with IVUS marking of the true ostium taking place (white asterisk). Panel B: The slit-like compression of the LMCA from the PA. Panel C: The aorto-ostial region of the LMCA. The Sepal wire enables the guiding catheter to be withdrawn from the LMCA ostium, and Ao cusp injection allows identification of relevant anatomical landmarks. Additionally, fine positioning of the stent can be undertaken, because the anchor provided by the Sepal wire prevents the guiding catheter from being “sucked” into the LMCA when one pulls back with the stent to cover the ostium (Panel D shows optimal positioning of the stent according to IVUS marking).
Source: Puri R. J Am Coll Cardiol Cardiovasc Interv. 2012;7:697-707; reprinted with permission.
Other Roles for IVUS During PCI
IVUS has also been shown to be a useful adjunctive imaging technique for the performance of complex, peripheral arterial intervention, particularly for the crossing of chronic total occlusions. There is emerging evidence of the utility of IVUS for guiding percutaneous intervention of CTOs within the coronary vasculature. IVUS is being increasingly utilized to assist in the recognition of the true lumen, particularly when the first guidewire enters the subintimal space. Lower profile IVUS catheters have been specifically developed to be positioned over the subintimal guidewire.
In addition, IVUS has been successfully utilized during more complex techniques such as reverse controlled retrograde and antegrade tracking (Reverse CART), whereby the lesion is approached from both directions, and a balloon is advanced over the antegrade wire and dilated within the subintimal space, then permitting the IVUS catheter to be advanced and positioned subintimally. Under IVUS-guidance, the retrograde wire can then be manipulated from the subintimal space into the true lumen beyond the occluded segment. IVUS has also proven useful for better defining the true position of the ostium in order for accurate stent positioning. Furthermore, the IVUS transducer can also be used in such a way as to obtain the optimal angiographic view and for marking exact positions of interest.
Summary
IVUS remains an important tool for the modern-day interventional cardiologist. Below is a summary of recommendations from the authors:
- IVUS is critical for outlining the distribution and morphology of plaque. As a complementary technique to angiography, it is valuable in identifying the mechanism of ambiguous features seen upon angiography (eg, hazy lesions).
- IVUS is useful for assessing stent apposition — especially during complex stenting involving DES — to help reduce the incidence of stent thrombosis.
- The relationship between lesion structure/burden and “gold-standard” functional significance (FFR <0.80) is an evolving area of research, requiring prospective clinical validation. However, in the setting of left main stenoses, IVUS remains the trusted tool for assessing lesion significance, with a greater degree of concordance with FFR measurements. An IVUS-derived left main MLA of <6.0 mm2 is currently considered a safe cutoff for deciding upon a revascularization strategy based upon this lesion severity.
- IVUS is strongly recommended for the planning and undertaking of left main PCI. For a single-stent strategy across a distal left main lesion, one should aim for a post-procedure MLA at the circumflex ostium of >4 mm2 and >5.5 mm2 for a two-stent strategy to minimize restenosis rates, which invariably occur at the ostia of both daughter branches. Iterative post-dilatation should occur to achieve an MLA of >8.5 mm2 of the distal left main segment (main branch).
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Rishi Puri, MBBS, is a senior research fellow in the Atherosclerosis Imaging Core Lab at the Cleveland Clinic; James E. Harvey, MD, is chief interventional fellow at the Cleveland Clinic; Yu Kataoka, MD, is a senior research fellow in the Atherosclerosis Imaging Core Lab; E. Murat Tuzcu, MD, is a professor of medicine and vice chairman of the department of cardiovascular medicine at the Cleveland Clinic, and is an Editorial Board member of Cardiology Today Intervention.
Disclosure: Drs. Puri, Harvey, Kataoka and Tuzcu report no relevant financial disclosures.