Dublin-based Medtronic plc has won an investigational device exemption for its Harmony transcatheter pulmonary valve, after completing an early feasibility study of the device in patients with congenital heart disease (CHD). According to cardiologist Lee Benson, a professor of pediatrics at the University of Toronto, Harmony should prove to be "a game-changer for this very large patient population," but he also said more sizes of the device are needed for these patients.

Medtronic unveiled data from an early feasibility study of the Harmony valve at TCT. That study, which initially enrolled 20 patients at three sites in the U.S. and Canada, demonstrated improved hemodynamics from baseline and "consistent valve performance at one year," according to Medtronic. The Harmony is an evolution of the company's Melody transcatheter pulmonary valve, which the FDA approved in early 2015.

Medtronic said Harmony is designed to address right ventricular outflow tract anomalies in four out of five patients who have undergone surgical repair or replacement of the pulmonary valve earlier in life. The Melody valve has been implanted in more than 10,000 patients across the globe, Medtronic said, and 18 of the 20 patients enrolled in the feasibility study were followed to five years. In this group, right ventricular end diastolic volume fell from an average of 284 to 195 milliliters at one year, and Medtronic said no clinically significant paravalvular leaks were observed.

Benson, who was involved in the feasibility study for the device, told Medical Device Daily that the Harmony at present comes in only one size, but the pulmonary valves in this patient population are possessed of "very peculiar architectures." He said the most difficult part of the research was identifying candidates who would be appropriate for the size of the valve that was designed for the feasibility study.

"What we learned is you need more sizes," Benson said. Three or four different device diameters would probably suffice, he said. Also, patients had to be screened for a pulmonary valve annulus for which the device would be appropriate. The IDE study will likely entail the use of only one valve size, the same as used in the feasibility study, Benson said.

Benson said such valves can be implanted via a blood vessel in the neck, but the valves in the feasibility study were all delivered via the femoral artery. He said the average age of patients in the study was probably 25, but they ranged in age from 18 to 80.

As for device durability, Benson remarked that the first Melody device was implanted in 2000, and those units have proven durable to date, so 16 years is not an unreasonable prediction for the Harmony. "Whether it last for 15 years or 20 years and you need another procedure, that's well within the expectations of the management profile" for this patient group, he said. Benson also said the device should prove amenable to a valve-in-valve approach as well.

The IDE study is expected to entail five-year follow-up and post-market surveillance. Benson said any device that can help a patient "avoid an open heart surgical procedure or a series of open heart surgical procedures, you've changed their life."

The Harmony and the Melody valves are different in some respects, Benson said, but anyone who has implanted the Melody "should be able to learn the techniques fairly quickly" for implanting the Harmony. While there are a few differences in terms of technique, Benson said, "getting the valve in the right spot is probably not as much of a problem as finding the right combination of device and anatomy." He said the only blood thinner needed is low-dose aspirin.

Incidence too high for HDE, but coverage lacking

The interest in treating a damaged pulmonary valve is not limited to Medtronic, but estimates of the prevalence of the underlying condition seem to vary somewhat. In any event, Medicare coverage seems to be lacking for some uses of pulmonary valve replacement, which seems to hold true for private payers as well.

In the June 2002 issue of the Journal of the American College of Cardiology, Hoffman and Kaplan noted that various studies have returned figures for congenital heart disease ranging from four to 50 per 1,000 live births. Another figure cited in this review is 19 per 1,000 live births when the count includes what the authors characterized as "trivial" lesions. The authors also pegged the incidence of tetralogy of Fallot, a congenital condition often handled with implant of a replacement pulmonary valve, at 421 per million live births, a figure that represents the mean arrived at by an analysis of more than 40 studies.

However, the Centers for Disease Control and Prevention said there are about 4 million U.S. live births each year, suggesting there are only about 1,680 potential patients for a device like the Harmony for this diagnosis annually, a number that could be handled via a humanitarian device exemption (HDE), which is good for 4,000 patients a year.

Still, valve replacement might be presumed to be an option for at least one of the four conditions subsumed in the tetralogy of Fallot diagnosis, which includes pulmonary stenosis. Hoffman and Kaplan noted that the 39 studies they saw about the incidence of this condition delivered a mean of 729 cases per million. Assuming these cases are separated from the tetraloty of Fallot group, this delivers far more than the 4,000-case maximum under the HDE program.

The coverage and reimbursement picture is no model of clarity, either. CMS has offered no coverage determination – or even an ongoing coverage analysis – for any kind of pulmonary valve replacement device, and a June 21 coverage summary by Unitedhealthcare stated that as of that date, two Medicare administrative contractors had declared the device/procedure either non-covered or not reasonable and necessary.

For its part, Aetna, of Hartford, Conn., covers pulmonary valve replacement for treatment of dysfunctional right ventricular outflow tract conduits, assuming the valve is stenotic, but the insurer also said the device is not covered for failed bioprosthetic pulmonary valves, which describes what many of these congenital heart defect patients already have in their chests by the time the Harmony device becomes an option.