Calcium Conundrum: New Scores, Research Aim to Boost Outcomes in PAD Interventions

LAS VEGAS, NV—Deep-dive research is helping to further the understanding of how calcium appears in the peripheral arteries and how operators can best deal with it when trying to get and keep vessels open. In a session at VIVA 2019 last week, the focus was on elevating the clinical science to shed much-needed light on an increasingly common clinical problem.

“We all hate calcified plaque,” noted Patrick Geraghty, MD (Washington University Medical School, St. Louis, MO), during his presentation. “It’s difficult to cross and efface, with high embolic risk and stent fracture risk and poor outcomes.” Vessel calcification is also associated with high-risk phenotypes that typically are excluded from clinical trials, such as patients with end-stage renal disease and diabetes, yet these individuals make up a significant proportion of real-world practice.

Although suspicion is high that calcification impacts drug uptake and although uptake “clearly matters,” Geraghty said the process is difficult to document. He also noted that none of the pivotal RCTs of paclitaxel drug-coated balloons (DCBs) and stents, where drug uptake is in question, performed structured calcium risk assessments, although he suggested post hoc analyses may be possible.

Research by Jihad A. Mustapha, MD (Michigan State University, East Lansing), has shown that calcium in the peripheral arteries has some common patterns of presentation that can include either “dusty” microcalcifications that cannot be visualized on high-sensitivity imaging, “lumpy” clumps of calcium, or a combination of both. When calcification is severe, Mustapha said, smooth-muscle cells lose their nuclei and become indistinguishable from surrounding fibrous tissue.

Defining ‘Severe’ and Improving Prediction Ability

Session co-moderator Krishna J. Rocha-Singh, MD (Prairie Heart Institute, Springfield, IL), pointed out that “one man’s ceiling is another man’s floor when it comes to severe calcium.” In a presentation on ways to unify definitions and better assess treatment of complex calcified lesions, he said VIVA has been at work to create a scoring system tied to clinical outcomes that would help operators better estimate their chances of success with DCB therapies in patients with varying degrees of calcification. To do this, they accumulated over 1,100 deidentified images from DCB core lab-adjudicated angiograms of patients enrolled in the IN.PACT and ILLUMENATE randomized trials and registries. Together with patient demographics, procedural details, and 12-month data, they developed a statistical model using vascular calcification as a continuous variable to predict both acute procedural success and clinical results through1 year for DCBs in superficial femoral artery disease.

We all hate calcified plaque. Patrick Geraghty

Although VIVA is still in the process of validating this new calcium score, Rocha-Singh said the suggestion is “that if you had a greater than 50% summation of bilateral calcification, that this was predictive of both acute procedural failure requiring a stent implant, and loss of primary patency at one year.” But, he added, “calcium and the company it keeps, meaning [chronic total occlusions], is also very predictive of failure, not surprisingly.” Ongoing assessment of the VIVA Calcium Score, he said, may facilitate a unified assessment of how different degrees of calcification impact the clinical efficacy of antimitotic drugs and help refine the definition for severe calcification.

Furthermore, interim data from the VIVA-sponsored REALITY study, which is assessing outcomes following adjunctive use of directional atherectomy and DCB in significantly calcified and symptomatic PAD patients, indicates that directional atherectomy as a debulking method for long, complex calcified lesions may reduce the need for provisional stent use and improve patency, Rocha-Singh noted.

Mustapha added that histopathology studies done in cadavers are helping to shed light on how calcium accumulates in the peripheral arteries of diabetic patients. This early work provides some suggestion that interventions aimed at tight control of diabetes, hyperlipidemia, and blood pressure may prevent the calcification from accumulating. Additionally, the novel Temporary Spur stent system (Reflow Medical) shows promise in patients with mild to severe calcification, Mustapha noted. Used before DCB deployment, he said, it is able to penetrate the vessel without perforating it or causing unnecessary trauma and allowing for good patency rates after delivery of the balloon.

Another possibility for dealing with calcification, noted Geraghty, is the Bullfrog (Mercator MedSystems), which allows for precision tissue injection targeting that may make it possible to enhance drug uptake without needing to remove the calcium from the arteries.