Melody Valve Yields Good Long-term Results, Especially With Pre-Stenting
Longer-term clinical and hemodynamic outcomes are generally positive following transcatheter pulmonary valve replacement with the Melody valve, according to a study published online May 5, 2015, ahead of print in Circulation. Endocarditis remains a concern up to 7 years after the procedure, however.
John P. Cheatham, MD, of Nationwide Children’s Hospital (Columbus, OH), and colleagues looked at data from the US investigational device exemption trial for the Melody device (Medtronic), which enrolled 171 pediatric and adult patients (median age 19 years) with RV outflow tract (RVOT) conduit obstruction and/or regurgitation. The current analysis included the 148 patients who were discharged with a Melody valve in place.
As seen in prior studies, the procedure substantially reduced pulmonary regurgitation. On the discharge echocardiogram, regurgitation was absent or trivial in 140 patients and mild in 5 (the valve was not visualized in the remaining 3 patients). There was also a drop in the mean Doppler RVOT gradient from 33 to 17 mm Hg (P < .001). Even so, at discharge, the gradient was > 20 mm Hg in 33% of patients and > 25 mm Hg in 12%.
During a median follow-up of 4.5 years (range, 0.4-7 years), 4 patients died—1 from multisystem failure resulting from endocarditis/sepsis and 3 from causes not deemed related to the Melody valve (1 from respiratory and 2 from unknown causes). Estimated survival at 5 years was 98%.
Overall, 32 patients underwent RVOT reintervention, mostly for obstruction (27 patients, including 22 with stent fracture). Another 3 patients underwent reintervention for endocarditis and 2 for RV dysfunction. Eleven patients had the device explanted during follow-up.
At 5 years, 76% of patients remained free from reintervention and 92% were free from explant. Factors associated with valve reintervention included use of a homograft conduit and having a conduit angiographic:nominal diameter ratio < .65, a discharge RVOT gradient > 25 mm Hg, and preimplant moderate-to-severe regurgitation. Use of pre-stenting was tied to a lower risk of reintervention (HR 0.29; 95% CI 0.13-0.67).
During follow-up, Melody valve stent fracture occurred in 50 patients, with type II fracture—defined as a compromise of stent integrity—in 25. Freedom from any stent fracture and type II fracture at 5 years was 61% and 83%, respectively. The risk of reintervention after a diagnosis of stent fracture was greater among patients with a higher discharge RVOT gradient (HR 1.07 per mm Hg; 95% CI 1.02-1.13) and an angiographic:nominal conduit diameter ratio < .65 (HR 4.2; 95% CI 1.4-12.2).
Among the 113 patients who survived to the end of follow-up without needing reintervention, RVOT gradient had not changed from early after the procedure. Only 1 patient had more than mild pulmonary regurgitation, and nearly all patients were in NYHA class I or II.
The most noteworthy adverse event during follow-up was definite/presumed endocarditis or bloodstream infection, which occurred in 14 patients, 5 of whom underwent reintervention within 3 months of diagnosis.
Infection and endocarditis are therefore “clearly a high-priority issue for ongoing investigation and will continue to be a focal point in analyses of this technology,” the authors write.
Changes in Practice, Outcomes Over Time
The performance of Melody valve implantation evolved during the conduct of the trial, which enrolled patients from January 2007 through January 2010. For example, conduit pre-stenting was not allowed during the first 35 implants. Thus, placement of a new pre-stent occurred in only 10% of the first 50 patients, with the percentage increasing to 54% of the next 50 and 42% of the final 50. Overall, pre-stenting was used in 36% of patients.
Other changes included an increase in the proportion of patients who underwent the procedure with the largest 22-mm delivery system, a decrease in use of the smallest 18-mm system, and a decline in postimplant dilation of the Melody valve.
“These differences corresponded to less complete relief of RVOT obstruction and shorter freedom from [stent fracture] and reintervention in the first 50 patients than those enrolled later,” Dr. Cheatham and colleagues write.
“Because this series represents the first prospective multicenter trial, and the first experience with [transcatheter pulmonary valve replacement] in the [United States], the results in the earliest patients… reflect a naive experience,” they continue. “Thus, although the data provide important insights, they are not representative of contemporary best practices, which include maximal relief of RVOT obstruction and, in most cases, implantation of one or more conduit pre-stents.”
Although the study will “serve as a landmark” because of its long follow-up, they say, “the freedom-from-event analyses of this cohort almost certainly overestimate the risk of [stent fracture], reintervention, and explant relative to contemporary practice.”
Editorialist Christopher J. Petit, MD, of Children’s Healthcare of Atlanta (Atlanta, GA), writes, “In contrast to reports of surgically implanted pulmonary valves, this study indicates that the Melody valve remains nonstenotic and nonregurgitant up to 7 years after implantation.
“The ramifications of such promising midterm results are important,” he says. The study “allows the clinician to more confidently counsel families when considering [transcatheter pulmonary valve replacement] and likewise gives our surgical colleagues good reason to implant conduits and valve prostheses compatible with future Melody utilization.”
Robert J. Sommer, MD, of Columbia University Medical Center (New York, NY), told TCTMD in an email that “the most exciting part of this study is the lack of valve stenosis and insufficiency late after implantation.
“With surgically implanted valves in children, there is a very high rate of failure over the first several years, usually in the form of valvular insufficiency,” he continued. “With the Melody, there is almost no rate of valve regurgitation outside of the devices that fractured early in the experience (prior to pre-stent implantation).”
Dr. Sommer explained that the use of pre-stenting has solved the problem of Melody valve stent fracture.
“If there is no recoil of the stent after deflation of the balloon, the Melody is implanted inside the stent,” he said. “If there is conduit recoil, a second bare-metal stent is placed inside the first, further strengthening its resistance to external compression. This can be repeated several times until a sturdy platform is achieved for the Melody, one which will be free of external compressive forces.”
Dearth of Pediatric Options
In his editorial, Dr. Petit highlights the disparity between adult and congenital valve technology.
“It is worthwhile, yet sobering, to compare the experience of a child with tetralogy of Fallot to that of an adult with acquired aortic valve disease,” he writes. “In the United States, a child with pulmonary valve failure might be fortunate to be among the subset of patients with suitable anatomy for the only FDA-approved percutaneous valve option [Melody]. Even so, that child would face a certain future of regular valve replacements. On the other hand, an adult in 2015 with acquired aortic stenosis may undergo implantation of 1 of 5 [TAVR] devices in the United States, or 1 of 7 devices in Canada or Europe.”
Dr. Petit questions how advancements in adult technology will eventually benefit patients with congenital heart disease, noting that despite the existence of the FDA’s Humanitarian Device Exemption pathway, which is meant to “incentivize industry to manufacture devices for areas of unmet clinical need,” economic obstacles remain to developing pediatric devices.
“Thus, in 2015, the congenital heart disease community continues to lag behind the adult cardiac world, where advancements and modifications can be more quickly studied and implemented,” he says. “The current study demonstrates the value of transcatheter valve implantation for treatment of congenital heart disease. One hopes that the Melody valve, despite its incredible success and durability, becomes the first of many transcatheter options for children with valve failure.”
1. Cheatham JP, Hellenbrand WE, Zahn EM, et al. Clinical and hemodynamic outcomes up to 7 years after transcatheter pulmonary valve replacement in the US Melody valve investigational device exemption trial. Circulation. 2015;Epub ahead of print.
2. Petit CJ. Pediatric transcatheter valve replacement: guests at our own table [editorial]? Circulation. 2015;Epub ahead of print.
- The study was sponsored by Medtronic.
- Dr. Cheatham reports serving as a consultant to Medtronic and NuMED and as a Melody valve investigator and/or proctor.
- Drs. Petit and Sommer report no relevant conflicts of interest.