Late and Early Results in Tune for Melody and Harmony Transcatheter PVs

Two reports, covering two different transcatheter pulmonary valves for separate yet related indications, reassure that an evolving field is headed in the right direction, with options expanding to a wider population of patients with congenital heart disease.

Transcatheter pulmonary valves (TPVs) placed within an existing dysfunctional right ventricular outflow tract (RVOT) conduit or bioprosthetic pulmonary valve show good long-term results, according to 10-year follow-up from the Melody (Medtronic) investigational device exemption (IDE) trial.

For the Harmony transcatheter pulmonary valve (Medtronic), 6-month data from the pivotal trial of show positive signs for a target that has proven to be more elusive: pulmonary regurgitation (PR) in patients who’ve undergone RVOT surgery for congenital heart disease but not received a prior valve or conduit.

Both reports came out during the 2020 Society for Cardiovascular Angiography and Interventions (SCAI) virtual meeting.

Thomas K. Jones, MD (Seattle Children’s Hospital, WA), who presented the Melody IDE data, pointed out to TCTMD that, back in 2000, the device was the first transcatheter valve to be implanted into a human patient.

“One of the celebratory aspects of this is that [Melody] represents a new paradigm in heart treatment that now has [grown into] this exploding number of patients treated worldwide, especially for aortic valve disease. But it all began with the congenital heart population in treating the pulmonary valve position,” he commented. As such, “this is the first and only long-term transcatheter heart valve study that’s ever been performed. Ten-year data is difficult to come by, and prospectively enrolled 10-year data is important.”

Christopher J. Petit, MD (Children's Healthcare of Atlanta, GA), agreed that the long-term follow-up is welcome. For clinicians who’ve implanted Melody valves over the years and tracked their outcomes, “there’s always been sort of an understanding of how our individual patients are doing. But certainly in the aggregate to have this data and have it be the entirety of all the initial 171 patients who were enrolled 10 years down the line, it’s very helpful,” he told TCTMD.

Melody IDE Trial

For the Melody IDE trial, researchers enrolled 150 patients whose median age was 19 years (47% were younger than 18). Half had originally been diagnosed with Tetralogy of Fallot. Pulmonary regurgitation was the primary indication for 53%, RVOT obstruction for 26%, and a combination of both for 21%.

By 10 years, 90% of these patients had survived. Most (73%) had no or trace amounts of PR, while 25% and 3% had mild or moderate PR, respectively. An even higher percentage were NYHA Functional Class I (78%), with 22% in Class II. Freedom from repeat surgery was 79%, and freedom from catheter reintervention was 72%.

The primary endpoint of the study was freedom from TPV dysfunction (reoperation, catheter reintervention, or hemodynamic dysfunction consisting of moderate or greater PR and/or mean RVOT gradient > 40 mm Hg). This was met by 54% of patients by 10 years.

“That compares quite favorably to the experience with surgically implanted valves,” Jones said.

Older patients seem to fare better, he pointed out. Specifically, 65% of adults were free of TPV dysfunction at 10-year follow-up, as compared to 47% of pediatric patients. This is because “they’re continuing to grow. So their somatic growth at some point outstrips the size of the valve that they have implanted,” Jones said, adding that late endocarditis is also a little more common in children.

Overall, endocarditis related to the TPV occurred in 19% of patients, amounting to an annualized event rate of 2% per patient-year. Major stent fracture increased only slightly between 5 and 10 years, from 15% to 16% of patients.

“The Melody valve fulfills its intended design goal of prolonging the useful life of surgically implanted RVOT conduits and bioprosthetic valves and reducing the lifetime burden of repeat open heart operations,” Jones concluded in his SCAI presentation.

Melody’s use hasn’t been static—as the therapy matured over the decade, the need for prestenting became more widely known, Jones told TCTMD. It’s also become used in valve-in-valve interventions for tricuspid or mitral disease. And finally, he added, operators can use a hybrid surgical approach or, less commonly, surgical implantation to now allow even younger children to receive a Melody device.

Looking ahead, Medtronic is developing a next-generation balloon-expandable bioprosthetic TPV that will be available in larger sizes than Melody, which has an internal diameter of 20 or 22 mm, he said.

“The big takeaways,” said Petit, “are that there is a pretty decent rate of reintervention at 10 years out.” For patients below 22 years old, 52% were free from reintervention; for patients 22 or older, this rate was 74%. “And that’s not surprising,” he said, observing that stenosis and other issues can arise. Another key finding, Petit continued, is that endocarditis risk isn’t just “early, but it’s constant. And it’s steady throughout those 10 years.”

Harmony Pivotal Trial

John P. Cheatham, MD (Nationwide Children's Hospital Heart Center, Phoenix, AZ), who presented the Harmony pivotal trial results, explained that of the patients who initially undergo RVOT surgery, 75% don’t receive a conduit or bioprosthetic valve at the time. These are the individuals who, as they develop PR over the years, are the intended recipients of Harmony. “It’s a bigger population base that has this particular condition,” he said.

But what’s been challenging, Cheatham told TCTMD, is being able to design a TPV that can deal with anatomic variations across patients—resulting from the different RVOT surgeries they’d undergone at a young age and how they had healed—as well as the dynamic shape and movement of the right ventricle. Harmony’s first iteration was implanted in a patient back in 2009; since then, though, its design has evolved in order to address these “engineering challenges,” said Cheatham.

In their pivotal trial, Cheatham et al include data on three Harmony generations: the initial 22-mm valve used in an early feasibility study; a subsequent 25-mm version that’s shorter in length, has wider diameters on its inflow and outflow ends, and is designed to treat a broader range of patients; and the most-recent 25-mm version that was modified to make implantation more predictable.

“Severe PR after surgical correction of RVOT anomalies remains an important hemodynamic abnormality and a challenge to correct using transcatheter technologies,” Cheatham told SCAI viewers.

Six-month data are available for 38 patients (out of the original 40) given the first two Harmony designs, and 1-month data are available for 10 who received the latest design.

Among the 50 total patients (median age 28 years, 38% women), 92% had originally been diagnosed with Tetralogy of Fallot, 6% with pulmonary stenosis, and 2% with pulmonary atresia with intact ventricular septum. Pulmonary regurgitation was severe for 94% and moderate for 6%.

At 30 days, the primary safety endpoint of freedom from procedure- or device-related mortality was 100%. Efficacy was defined as no valve interventions plus mean RVOT gradient ≤ 40 mm Hg and PR fraction < 20% by cardiac magnetic resonance or PR < moderate by echocardiography, with a performance target of 75%. Depending on which of the device iterations were included, 6-month efficacy was 89% to 91%. At 6 months, mean RVOT gradient was 14.6 mm Hg, residual moderate/severe PR was 6%, and the rate of moderate paravalvular leak was 3%.

The most common adverse events were ventricular tachycardia (18%), minor paravalvular leak (10%), minor hemorrhage (10%), and ventricular premature beats (8%).

“The results we’re very happy with so far. It certainly met its safety index and efficacy that it needed to meet,” Cheatham told TCTMD. These Harmony data are currently in the process of being submitted to the US Food and Drug Administration for premarket approval, he said. A continued access study on the 22-mm and most-recent 25-mm versions is ongoing.

As of now, the only two FDA-approved TPVs are Melody and the Sapien XT (Edwards Lifesciences).