PARIS – A novel therapeutic ultrasound-based technology known as lithoplasty is turning heads in interventional cardiology and vascular medicine because it addresses the bane of interventionalists’ existence: complex, heavily calcified coronary and peripheral artery lesions.

“Calcification is something we deal with every day in interventional cardiology. It makes the procedures more expensive, longer, and in fact several recent studies have shown that the complication rate for calcified lesions is higher than for any other lesion subtype. Calcification is the next big thing that we’re trying to take on in interventional cardiology,” Todd J. Brinton, MD, observed at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

As an example of the problems calcified lesions create, he cited an analysis of 6,855 acute coronary syndrome patients in whom percutaneous coronary intervention was performed in the ACUITY and HORIZONS-AMI trials. The 1-year rate of major adverse cardiovascular events (MACE) was 12.9% in those with no or mild coronary calcification, 15.3% with moderate calcification, and 19.9% with severe calcification. Moreover, the 1-year cardiac death rate of 4% in patients with severe calcification was more than twice that in those with no or minimal calcification (J Am Coll Cardiol. 2014 May 13;63[18]:1845-54).

At EuroPCR, he presented the results of DISRUPT CAD, a seven-center study in which 60 patients with heavily calcified coronary lesions underwent lithoplasty in order to facilitate stent placement. The study met all of its safety and performance endpoints. As a result, the week prior to EuroPCR the European regulatory agency granted marketing approval for Shockwave Medical’s coronary lithoplasty system; the indication is for coronary vessel preparation prior to stenting. A large phase III U.S. trial aimed at gaining FDA approval is planned.

Moreover, on the basis of the earlier favorable DISRUPT PAD trial, lithoplasty has already been approved for treatment of peripheral artery disease (PAD) in Europe since late 2015 and by the FDA since September 2016. Now underway is DISRUPT PAD III, a large postmarketing randomized trial comparing lithoplasty with conventional balloon angioplasty in patients with heavily calcified PAD, added Dr. Brinton, an interventional cardiologist at Stanford (Calif.) University and cofounder of Shockwave Medical.

Lithoplasty is a potentially transformative technology which he described as “lithotripsy inside a balloon.” Lithotripsy has an established 30-year track record for the safe treatment of kidney stones. However, lithotripsy utilizes focused ultrasound, while lithoplasty relies upon circumferential unfocused therapeutic ultrasound delivered by miniaturized emitters placed inside a 12-mm intravascular balloon. The balloon is crossed to the target lesion, inflated to a modest pressure of 4 atmospheres, then the operator delivers lithoplasty pulses lasting over 1 microsec in duration at a rate of 1/sec for 10 seconds in order to fracture the thick intramedial calcium plaque, allowing the lesion to open up and thereby normalize vessel compliance.

“Once you’ve cracked the calcium you can easily dilate the lesion. It’s the calcium that’s restricting the ability to dilate. The real fundamental need here is to maximize acute gain to get really good stent apposition. We’re trying to get expansion,” the cardiologist explained.

That was readily achieved in the DISRUPT CAD study. The 60 participants had reference vessel diameters of 2.5-4.0 mm, with an average target lesion length of 20 mm. The calcification was heavy, covering on average 270 degrees of the vessel circumference as measured by optical coherence tomography, with an average calcium thickness of 0.97 mm and a calcified segment length of 22.3 mm.

The mean stent expansion was 112%. The minimum luminal diameter improved from 0.9 mm pretreatment to 2.6 mm post treatment, for an acute gain of 1.7 mm. The amount of acute gain was similar across the full range of vessel diameters.

The mean diameter stenosis went from 68% pretreatment to 13% post-treatment.

The primary safety endpoint was the 30-day rate of MACE, defined as cardiac death, MI, or target vessel revascularization. The rate was 5%, consisting of 3 patients with mild non–Q-wave MI defined by creatine kinase–MB elevations more than three times the upper limit of normal. The 6-month MACE rate was 8.5%, which included the three non–Q-wave MIs plus two cardiac deaths not related to the procedure or technology.

Final angiographic results adjudicated in a central core laboratory showed no perforations, abrupt closures, slow or no reflow events, or residual dissections. These are complications commonly seen with debulking devices such as rotational or orbital atherectomy, Dr. Brinton noted.

The primary performance endpoint in DISRUPT CAD was clinical success, defined as a residual stenosis of less than 50% post PCI with no in-hospital MACE. This was achieved in 57 of 60 patients, or 95%. The device was successfully delivered to the target lesion with subsequent performance of lithoplasty in 59 of 60 patients. An even more flexible and deliverable device will be released in the coming year, according to the cardiologist.

“I’d say the take-home is that the disease has changed,” Dr. Brinton commented. “It’s not the same disease that we had when Gruentzig did his first balloon angioplasty. These lesions are more calcified, more complex, yet for the most part we use the same balloon we’ve been using for the last 40 years. So lithoplasty is really an attempt to modernize the therapy in a new patient subset we now take care of who are much more complicated than the patients we originally took care of.”

“The reality is, we’re having difficulty taking care of these patients. For myself as an interventionalist, it’s not uncommon to look around the table and see a massive amount of tools when we’re doing these complex cases. Lithoplasty is intended to bring the simplicity. I would say it’s not necessarily to make the best operators better, it’s to bring all operators up to the ability to take on these complex lesions that are now usually reserved for high-volume centers that can do debulking,” he added.

Session cochair David R. Holmes Jr., MD, of the Mayo Clinic in Rochester, Minn., pronounced lithoplasty “tremendously exciting.” He and the other panelists focused on questions of safety and potential collateral damage: Where does the calcified debris go? What are the effects of the unfocused sonic pressure waves on noncalcified plaque? How hot does the vessel get?

Dr. Brinton replied that thick calcium plaque is located mostly in the medial vessel wall and stays there after fracturing. That’s why distal embolization wasn’t an issue in DISRUPT CAD. In animal studies, even at 20 times the energy dose used in clinical practice, lithoplasty had no effect on softer, noncalcified plaque or normal tissue. Vessel temperature increases by about 1.2 degrees C during lithoplasty, which isn’t sufficient to cause injury or drive restenosis.

Elsewhere at EuroPCR, Alberto Cremonesi, MD, who chaired a press conference where Dr. Brinton presented highlights of DISRUPT CAD, declared lithoplasty is “in my mind a real breakthrough, not only for coronary disease but also for PAD.”

Is it possible that stand-alone lithoplasty could reduce the need for multiple stents in longer coronary lesions, instead making possible more focal stenting? asked Dr. Cremonesi of Maria Cecilia Hospital in Cotignola, Italy.

That’s one of several possibilities worthy of future investigation, Dr. Brinton replied. Lithoplasty might also facilitate the results obtainable with bioresorbable coronary scaffolds or drug-coated balloons, he added.

He noted that as cofounder of and a consultant to Shockwave Medical, he has a sizable financial involvement with the company.

bjancin@frontlinemedcom.com

Lithoplasty tames heavily calcified coronary lesions