DISRUPT CAD: Lithoplasty May Modify Dense Calcium in Coronary Lesions Before Stenting

PARIS, France—A novel device using lithoplasty, modeled after the technology used to break up kidney stones, is showing promise in the field of modifying calcified coronary lesions prior to stent implantation.

“The disease has changed. It's not the same disease that we had when Gruentzig did his first angioplasty. These [lesions] are more calcified, more complex, and yet we for the most part use the same balloon we’ve been using for the last 40 years. So lithoplasty is an attempt to really modernize the therapy,” said Todd Brinton, MD (Stanford University, Palo Alto, CA), who presented results of the DISRUPT CAD study at a Hot Line session here at EuroPCR. Brinton founded the company developing the technology.

The lithoplasty system (Shockwave Medical; Fremont, CA) is made up of a semicompliant balloon catheter, connector cable, and generator. When deployed, it releases pulsatile mechanical energy that causes microfractures in the calcium. The system has already shown feasibility in peripheral lesions.

For DISRUPT CAD, conducted at seven centers, Brinton and colleagues enrolled 60 patients with moderately and severely calcified de novo coronary lesions with a reference vessel diameter between 2.5 and 4.0 mm, at least 50% stenosis, and a length no greater than 32 mm. Mean lithoplasty inflation pressure was 6 atm and most patients received postdilatation. Device success was 98% and all patients had successful stent delivery.

Total acute gain was 1.7 mm and this was not affected by reference vessel diameter, “suggesting this was effective across the board,” according to Brinton. There were no distal embolizations postprocedure, and at 30 days there were no angiographic complications such as residual dissections, perforations, abrupt closures, slow flows, or no reflows, which can result from other debulking technologies like rotational or orbital atherectomy.

The average circumferential calcium was 270 degrees and the average calcium thickness was 0.97 mm, “so these are . . .  heavily calcified lesions and yet the acute gain was in line with what we see in traditional trials for acute gain, which is standard balloon angioplasty,” he explained.

Freedom from 30-day MACE was 95%, with three non-Q-wave MIs. By 6 months, there were two cardiac deaths.

“The lithoplasty balloon performance was excellent,” Brinton observed. “There was high acute gain with low residual stenosis that was all core lab-adjudicated. It was not independently reported at each center.”

Delving into the Details

In a panel discussion following the study presentation, session co-moderator David R. Holmes Jr,, MD (Mayo Clinic, Rochester, MN), asked about the fate of the fractured calcium over time.

“At 6-month follow-up, you see very, very different acoustic shadowing than you saw prior, so you’re getting fractures with the calcium,” Brinton responded. “I can’t say what happens in 6 to 10 years, but you can certainly see the acoustic window changing dramatically.”

Though this study looked at using lithoplasty to predilate for stent or scaffold placement, he continued, “I think it opens the door for lots of options, because we might even expand to areas like DCB in the coronaries, lots of different ways that we can take care of patients. The primary thing is you don’t need the radial force of the stent to accomplish what we’re trying to accomplish here.”

I think it opens the door for lots of options, because we might even expand to areas like DCB in the coronaries, lots of different ways that we can take care of patients. Todd Brinton

Panelist Olivier Muller, MD, PhD (University Hospital, Lausanne, Switzerland), asked if Brinton knew anything about how the temperature that the vessel reaches during lithoplasty might affect outcomes.

Other research has shown that temperature elevation can potentially injure the vessel wall, Brinton acknowledged. “We looked at this over and over again on the bench and in different water bath models and such. We’re getting about 1.2 to 3 degrees centigrade over the period of the treatment. This is one pulse per second. Because [of this], you have dramatic cooling between the actual lithoplasty pulses.”

Muller also asked about the potential effects of lithoplasty on noncalcified plaque. At this dose and 20 times the dose in animal models, Brinton said there were no differences in angioplasty alone and angioplasty with lithoplasty. “This is the same thing as taking a tuning fork up to a glass,” he explained. “The idea is these harmonic pulse waves actually resonate normal tissue just fine, . . . and the difference between these fractures and what you see on traditional rotoblator or orbital atherectomy or high-pressure ballooning is typically you see tears at the edge of the calcium where the tissue is attached to the calcium, which is why we get high levels of dissection. In this case, the fractures are in the center where it’s the most dense. You are actually fracturing directly through the calcium, which I think is what we’re trying to accomplish.”

Jackhammering vs Pressing

Commenting on the study for TCTMD, Spencer B. King, MD (Emory University School of Medicine, Atlanta, GA), said he has been intrigued by this technology for a while now “primarily because the mechanism of it is different from what we do with debulking and all these atherectomy things.” Likening the cath lab to a construction site, he said, “when you see [workers] breaking up the sidewalk, they don't do it by just pressing on it, they do it with a jackhammer. So the idea of cracking up the concrete has always been interesting.”

When you see [construction workers] breaking up the sidewalk, they don't do it by just pressing on it, they do it with a jackhammer. Spencer King

Since DISRUPT CAD only definitively shows feasibility and not safety or efficacy, he said the next logical step would be an IVUS-guided phase II randomized trial, potentially pitting lithoplasty against standard-of-care balloon angioplasty in heavily calcified lesions. Studies would also need to explore stent deployment measures, compare expansion metrics, and assess potential excess injury that could result in more proliferation, King commented.

Having seen lithoplasty done in person, King said it is “very convincing,” especially when the balloon opens at just 4 atm. “Then the question is, if you do that, is that giving you a better result, not just in this minute, but . . . in the longer-term follow-up?” In other words, would this necessarily translate into better outcomes than traditional angioplasty at 20 atm, he continued.

At some point, lithoplasty will have to be compared with rotational and orbital atherectomy, King predicted, adding that it would not be prudent to jump right into a trial like this now.

All in all, he said he is excited about this technology. “It's going at the concrete problem, hard calcified things, in a way that I've always felt we should find a way to do,” King concluded.