Postapproval Study Confirms Safety, Efficacy of Transcatheter Pulmonary Valve in Real World

Expanding on data from the Investigational Device Exemption (IDE) trial, a postapproval study confirms the short-term hemodynamic effectiveness of the Melody transcatheter pulmonary valve (TPV) in patients with right ventricular outflow tract (RVOT) conduit dysfunction.

First presented in March 2014 at the American College of Cardiology/i2 Scientific Session, the results were published in the November 2014 issue of JACC: Cardiovascular Interventions. 

Aimee K. Armstrong, MD, of the University of Michigan C.S. Mott Children’s Hospital (Ann Arbor, MI), and colleagues enrolled 120 patients (mean age 19.9 years; 65.8% male) with a stenotic and/or regurgitant conduit at 10 centers from July 2010 to July 2012. Of these, 100 patients received the Melody valve (Medtronic) for at least 24 hours, with a femoral venous approach used in 87%. 

Reasons for not receiving a valve included: risk of coronary artery compression (n = 6), conduit not suitable for implant (n = 4), criteria not met during catheterization (n = 4), relief of conduit stenosis by angioplasty (n = 3), need for surgical repair of another heart condition (n = 1), and risk of branch pulmonary artery stent compression (n = 1).

Acceptable Hemodynamic Function for Most at 6 Months 

The Melody device consists of a valved segment of a bovine jugular vein sewn within a balloon-expandable stent. It was approved in 2010 by the US FDA to treat dysfunctional circumferential RVOT conduits ≥ 16 mm at initial implantation.

The device was approved under the Humanitarian Device Exemption (HDE) program, which supports the development of medical devices for diseases or conditions affecting fewer than 4,000 people per year. The HDE program allows the FDA to approve a device for limited use if there is reasonable assurance of safety and if the probable benefit to health outweighs the risk of injury or illness. As a condition of the Melody approval, Medtronic was required to conduct 2 postapproval studies to assess long-term risks and benefits and to evaluate the physician specialization needed to perform the procedure. The current postapproval study adds additional centers and patients to those that participated in the IDE. 

Unlike the 5-center IDE trial, the postapproval study had no limitations on concomitant procedures. In all, 84% of patients undergoing valve implantation had concomitant interventional procedures, 78% of which involved stenting.

The procedural success rate was 98.0%, and there were no procedure-related deaths. At 6 months, 96.7% of the implanted cohort with evaluable data had acceptable hemodynamic function (primary endpoint), with 87 patients having a mean RVOT gradient ≤ 30 mm Hg and none having moderate or worse pulmonary regurgitation, needing catheter-based reintervention, or requiring surgical RVOT conduit replacement. 

Similarly, the rate of acceptable hemodynamic function at 1 year was 94.3% for the implanted cohort with evaluable data. The percentage of patients in NYHA functional class I increased from 35% at baseline to 89% at 1 year. Decreases in echocardiographic mean RVOT gradient were seen, from 33.3 ± 14.1 mm Hg preimplantation to 15.0 ± 9.9 and 15.1 ± 7.1 mm Hg at 6 months and 1 year, respectively.

Additionally, 1-year rates of freedom from catheter- or surgery-based reintervention and TPV dysfunction were 98.0% and 96.9%, respectively, and no patients had moderate or severe pulmonary regurgitation. Echocardiographic tricuspid regurgitation also improved over the study period (P < .0001). 

Among 8 serious adverse events related to the device, 3 were endocarditis that resolved with antibiotics. Procedure-related serious adverse events occurred in 13.3% by 1 year. The most common was a confined conduit tear (n = 6).

Stent fracture occurred in 7 patients, with only 1 requiring reintervention for major stent fracture. The other 6 patients whose stent fractures were minor were all prestented, and none had TPV dysfunction at 6 months or 1 year. 

Rise in Complications Unsurprising

Dr. Armstrong and colleagues note that the adverse event rate seen in the postapproval study is more than double that of the 6% rate seen in the IDE trial. Among possible reasons for this, they suggest, is that allowing concomitant interventions in the postapproval study lengthened procedure time, thus increasing the risk for complications or adverse events. Unlike the IDE trial, the postapproval study also had no age or weight limit, which is important, they say, because 1 of the 2 pediatric patients in whom implantation was unsuccessful due to pulmonary hemorrhage before implantation would have been considered too small for the IDE trial. 

Overall, more procedural complications are to be expected in real-world studies, the investigators say, noting that their serious adverse event rates are comparable to those of an Italian multicenter prospective study (Butera G, et al. Catheter Cardiovasc Interv. 2013;81:310-316).

Dr. Armstrong and colleagues maintain that the postapproval study “confirms the strong performance of the Melody TPV achieved by real-world providers with results comparable to those of the US IDE trial” and demonstrates that the procedure “remains a less invasive alternative to surgical RVOT conduit replacement.” 

Represents a ‘Transformative Technology’

In an editorial accompanying the study, Carlos E. Ruiz, MD, PhD, and Chad Kliger, MD, MS, both of Lenox Hill Hospital (New York, NY), point out that, by counting only patients who received a valve, the adverse event rate rises from 13% to 16%. Like Dr. Armstrong and colleagues though, they say that postapproval studies of other technologies have also shown higher rates of complications as more challenging and complex cases are performed. 

“Overall, we applaud the authors in their report of this transformative technology that supports the use of the Melody [TPV] in the real-world setting—the Unchained Melody—to delay the time until repeat open heart surgery,” Drs. Ruiz and Kliger write. “The magnitude of the effect of the Melody TPV on the field of congenital cardiovascular interventions has been profound, with well over 3,500 patients implanted worldwide and rapidly expanding.”
 

1. Armstrong AK, Balzer DT, Cabalka AK, et al. One-year follow-up of the Melody transcatheter pulmonary valve multicenter post-approval study. J Am Coll Cardiol Intv. 2014;7:1254-1262.

2. Ruiz CE, Kliger C, et al. Transcatheter pulmonary valve implants: the unchained melody [editorial]. J Am Coll Cardiol Intv. 2014;7:1263-1265.

Disclosures:

• The study was sponsored by Medtronic.
• Dr. Armstrong reports receiving a research grant from Edwards Lifesciences.
• Dr. Ruiz reports no relevant conflicts of interest. 
  
• Dr. Kliger reports receiving speaker’s honoraria from Philips Healthcare and St. Jude Medical.

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