Arterial Deposition of Calcium and Outcomes of Peripheral Interventions: Is It Time to Redefine the Gold Standard?

ABSTRACT: Patients with severe peripheral artery disease and critical limb ischemia frequently present with multilevel disease characterized by variable densities of calcium deposits, which are underestimated by more than 50% during angiography. These calcified lesions are associated with an increased rate of complications and poor clinical outcomes due to their high resistance to angioplasty (the “gold standard”), generated by the heterogeneous deposition of calcium deposits along the different layers of the arterial wall. When these heterogeneous deposits are subject to increasing barometric pressures, the distribution of the pressure vectors is unpredictable with a tendency to follow the path of least resistance, increasing the risk of dissection, plaque rupture, embolization, and no-flow. In recent years with the advent of new technologies, we have learned that by modifying the architecture of these calcium deposits, the overall vessel wall resistance to barometric pressure is lessened and the pressure vectors are more homogenously distributed, thus decreasing the likelihood of adverse outcomes. This review attempts to condense the most recent and relevant data that support these physiologic principles while challenging the status quo of peripheral interventions as it appears that we are witnessing a change of paradigm where plaque and vessel wall modification, in conjunction with angioplasty and possibly drug delivery, may become the new gold standard.

VASCULAR DISEASE MANAGEMENT 2013;10(10):E208-E211

Key words: atherectomy, peripheral arterial disease, claudication

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Patients with severe peripheral artery disease (PAD) and critical limb ischemia (CLI) represent a growing segment of the population and of our daily practices. These patients tend to have multilevel disease characterized by its diffuse nature and the different densities of calcium deposits that are distributed along the length of the lesions (Figure 1). During angiographic evaluation of these patients, it is important to keep in mind that this modality (considered the “gold standard”) underestimates the severity of calcium deposition by more than 50%.¹ Despite advances in endovascular therapies, calcified lesions remain technically challenging and often place the operator face to face with the undesirable situation of having to perform high-pressure balloon angioplasty² in an effort to treat an undilatable or recalcitrant lesion. It is therefore not a surprise that calcified lesions are associated with a higher rate of flow-limiting dissections and bail-out stenting procedures, which in turn lead to less-than-optimal clinical outcomes.   

In recent years with the increased use of advanced imaging modalities, we have learned that the calcium deposition process spreads beyond the lumen and extends into the outer layers of the vessel wall, as far as the adventitia. We have also observed isolated intimal, medial, and adventitial calcium deposits, which can occur either independently of one another or in random combinations. The endovascular treatment for vessels with calcified features should remain under the umbrella of “high-risk complex revascularization” due to the high resistance to inflation that is generated by the variable calcium densities in the different layers of the vessel wall, creating unpredictable distribution of the force vectors, which tend to follow the path of least resistance, leading to an increased risk of dissection, plaque rupture, and embolization with ensuing no-flow phenomena. When the calcium deposits are modified, the overall vessel wall resistance is lessened and the paths of least and highest resistance become nearly homogeneous in all segments, therefore decreasing the likelihood of dissections and perforations.

The Diamondback 360 Orbital Atherectomy System (Cardiovascular Systems, Inc.) consists of a flexible coil-wound drive shaft with an abrasive crown that has a diamond-coated surface. Activation of the catheter results in progressive and predictable lumen enlargement by “intelligent differential sanding” which achieves plaque abrasion without barotrauma, intimal injury, or thermal injury by increasing the rotational speed of a given device size.

The crown has an eccentric shape, which shifts the center of mass away from the center of rotation, creating luminal gain by centrifugal force. Upon activation, the device generates an elliptical orbit in which the orbital diameter is determined by the crown diameter and the rotational speed.  There are three different types of crowns. 

The Solid Micro Crown (Figure 2) is designed for tortuous vessels and tight bends below the knee and ankle, with an increased mass (from the solid crown) for more effective sanding.

The Solid Crown (Figure 3) design has a larger mass and diamond-coated surface area and is intended for maximum calcium removal with shorter run times.

The Classic Crown (Figure 4) is the most flexible configuration and as such is designed for bends, ostial lesions, and below-the-knee interventions. By adding Tungsten (a heavier metal), the device rotates in a more eccentric and larger orbit, therefore increasing the orbital force for a higher level of plaque reduction. The Stealth electrical generator (Figure 5) allows rapid setup and is rather simple to use. 

After removing the calcified plaque and changing the compliance of the vessel wall, low-pressure balloon angioplasty can be used to finish the procedure safely. This principle has been used as the foundation in the design of the currently available studies supporting the use of this atherectomy modality.

Calcium 360

Calcium 360 was a randomized, prospective, multicenter study that evaluated orbital atherectomy (OA) + percutaneous transluminal angioplasty (PTA) vs PTA alone in 50 patients with infrapopliteal PAD. Estimates for freedom from target vessel revascularization (TVR) and all-cause mortality were 93.3% and 100% respectively in the OA + PTA group vs 80% and 68.4% (P= .01) in the PTA-only group. Proportional hazard models evaluating survival time vs status of residual stenosis determined a hazard ratio for major adverse events of 5.6 for patients with an acute postprocedure residual stenosis >30% (P =.01). The mean inflation pressure was 5.9 atm in the OA group vs 9.4 in the PTA alone group (P=.001). The lower rate of complications with OA can therefore be attributed to proper plaque modification and debulking, which allowed for better results with low-pressure balloon angioplasty.³

Compliance 360

Compliance 360 was designed as a multicenter, randomized, prospective registry that evaluated OA + low pressure PTA (up to 4 atm) vs PTA alone in 50 patients with calcified femoropopliteal lesions. Adjunctive stenting was needed in 8% in the OA arm vs 84% in the PTA alone arm (P<.0001). Mean maximum balloon pressure (a measure of lesion compliance) in the OA arm was 3.9 atm vs 9.1 atm in the PTA arm (P<.0001). Freedom from target lesion revascularization (TLR) (including acute adjunctive stenting) or restenosis at 6 months was met in 72.7% of the OA arm and 8.3% of the PTA arm (P<.0001). By 12 months, restenosis or repeat TLR occurred in 5 of 21 in the PTA arm (4 in-stent) and 5 of 20 in the OA arm (P=NS). In summary, compared to PTA alone, orbital atherectomy with low-pressure PTA leads to better acute luminal gain by improving lesion compliance with less need for adjunctive stenting when treating calcified femoropopliteal lesions. 

While freedom from TLR was superior for OA at 6 months, the patency rate at 12 months was comparable to PTA with a provisional stent strategy.⁴   

CONFIRM

CONFIRM is a registry series designed to evaluate OA in peripheral lesions in the lower extremities, as well as to optimize the technique with which OA is performed. It encompasses a total of 3,135 patients originally enrolled in either one of the three registries (CONFIRM I, II, and III). CONFIRM I evaluated the Diamondback 360; CONFIRM II evaluated the Predator 360, and CONFIRM III evaluated the Diamondback 360, Predator 360, and the Stealth 360. Eighty-one percent of lesions had moderate to severe calcification and the average preprocedural stenosis was 88% as adjudicated by the treating physician. Treatment with OA reduced stenosis from 88% to 35%. Final residual stenosis after adjunctive treatment (generally low-pressure PTA at a mean of 5.5 to 5.8 atm) averaged 10%. 

As iterations of the device progressed and data was collected, it was noticed that shorter spin times and the use of smaller crown sizes significantly decreased procedural complications including slow flow, vessel closure, and spasm. This key point drives home the message that the treatment should focus on plaque modification rather than on the acquisition of maximal luminal gain.⁵ This is a rather important point as the tendency is to fulfill the mantra “bigger is better.” As evidenced in the studies, orbital atherectomy is effective in the treatment of calcified lesions in both the femoropopliteal segment as well as below the knee.

When using this device, based on accrued data the right thing to do is to modify the plaque by using short runs (limited to 25 to 30 seconds) with a conservative crown sizing approach to avoid the potential complications including embolization (and the ensuing slow-flow and no-flow phenomena) as well as perforation (rarely seen unless deep debulking is performed in “popcorn” lesions and in lesions where the wire has gone into the subintimal space). 

When treating long, diffusely calcified, and heavily calcified lesions in the superficial femoral artery in patients with compromised outflow, it is advisable to consider the use of embolic protection. The Emboshield NAV6 Embolic Protection System (Abbott Laboratories) has been utilized (off label) with reported success. In order to use this system, the operator has to choose the ViperWire that has the 0.017˝ tip (instead of the more commonly used 0.023˝) in order to be able to accommodate the filter.

Overall, it can be stated that these orbital atherectomy studies share the lack of core lab adjudication of the angiographic data. However it needs to be acknowledged that the ability to treat calcified lesions followed by low-pressure PTA is a rather inviting concept thatprovides the same freedom from TLR as PTA with provisional stenting at 1 year. 

Conclusion

With these and the recent results of DEFINITIVE LE,⁶ it has become evident that balloon angioplasty may no longer be the standard of care for the treatment of PAD. If stand-alone balloon angioplasty is not sufficient for the treatment of peripheral vascular disease, is adjunctive therapy to balloon angioplasty the answer? We anxiously await the results of the ongoing combined-therapy studies. DEFINITIVE AR is an ongoing prospective combined-therapy atherectomy and drug-coated-balloon therapy trial for the treatment of peripheral vascular disease. LIBERTY 360° is a prospective, observational, multicenter, postmarket study that will enroll up to 1,200 patients at 100 sites in the United States, including 500 patients with claudication (Rutherford II, III), 500 patients with CLI (Rutherford IV and V) and 200 CLI patients with Rutherford VI who have been slated for amputation. LIBERTY 360° is the first study of its kind to specifically include this challenging population and will evaluate numerous parameters including procedural and lesion success, rate of major adverse events, duplex ultrasound findings, quality of life, 6-minute walk test, wound status, economic outcomes, and development of plaque burden assessment. Both of these trials will include core lab adjudication of angiographic and ultrasound data. Hopefully, the quality of the information obtained will be enough to provide clinicians with the information needed to make the soundest decisions when faced with patients with severe PAD and CLI. 

Editor’s Note: Disclosure:  The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Mustapha reports consultancy to as well as educational support, travel reimbursement, and research grants from Cardiovascular Systems, Inc. Dr. Diaz-Sandoval reports educational support, travel reimbursement, and research grants from Cardiovascular Systems, Inc. 

 Manuscript received July 31, 2013; provisional acceptance given September 9, 2013; final version accepted September 15, 2013.  

Address for correspondence: J.A. Mustapha, MD, Metro Health Hospital, 5900 Byron Center Ave. SW, Wyoming, MI 49519, United States. Email Address: jihad.mustapha@metrogr.org 

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