US Melody Transpulmonary Valve Trial - US Melody TPV Trial

Aug 02, 2010
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Medtronic Inc.
Date Published:
01/01/2010
Date Updated:
08/02/2010
Original Posted Date:
08/02/2010
References

Description:

The Melody pulmonary valve is a newer addition to the interventional armamentarium. Traditionally, the two options for patients with right ventricular outflow tract (RVOT) dysfunction and/or pulmonary regurgitation (PR) were medical management or surgical pulmonary valve replacement. The Melody valve represents a transcatheter approach to this problem.

The initial experience with 34 patients was reported recently, following which it received Food and Drug Administration approval. The current trial represents extended follow-up of an expanded cohort receiving the Melody valve.

Hypothesis:

The Melody valve would be safe and efficacious in patients with RVOT dysfunction and/or PR.

Study Design

  • Randomized

Patient Populations:

  • Age ≥5 years
  • Weight ≥30 kg
  • Original conduit diameter ≥16 mm
  • Echocardiographic RVOT conduit dysfunction
  • Patients classified as NYHA functional class II, III, IV: Doppler mean gradient ≥35 mm Hg or ≥moderate PR
  • Patients classified as NYHA I: Doppler mean gradient ≥40 mm Hg or severe PR associated with tricuspid valve annulus Z-score ≥2 or RV fractional shortening <40%
  • Number enrolled: 136
  • Median patient age: 19 years
  • NYHA class: I (16%), II (67%), III (16%), IV (1%)

Exclusions:

  • Active endocarditis
  • Major progressive noncardiac disease
  • Central vein occlusion or significant obstruction
  • Pregnancy
  • Intravenous drug abuse
  • Contraindication to MRI
  • Unable/unwilling to sign informed consent or comply with follow-up


The protocol was amended after the first 34 patients to allow the following patients:

  • Patients with contraindications to MRI
  • Patients in whom concomitant transcatheter interventions were indicated
  • Patients with a bioprosthetic valve not housed in a circumferential conduit as long as the manufacturer-specified inner diameter ranged from 18 to 20 mm

Primary Endpoints:

Safety:

  • Percentage of patients with procedure- or device-related mortality during 6 months of follow-up
  • Percentage of patients with procedure- or device-related adverse events during 6 months of follow-up

 

Procedural success:

    Percentage of patients with successful valve implantation, defined as:

  • Valve fixed within desired location 
  • RV-PA peak gradient measured by catheter <35 mm Hg 
  • Trivial or less PR
  • Freedom from valve explant 24 hours after implantation


Short-term effectiveness:

    Percentage of patients with acceptable valve function at 6 months, defined as: 

  • Pulmonary regurgitant fraction <20%
  • RVOT Doppler mean gradient ≤30 mm Hg

Secondary Endpoints:

  • Freedom from reintervention
  • Freedom from valve dysfunction

Drug/Procedures Used:

Conduit predilation was performed in all patients using a balloon ≥2 mm larger than the narrowest diameter of the conduit and <110% the original conduit diameter. If the balloon waist measured between 14 and 20 mm on subsequent low-pressure (≤8 atm) balloon sizing, Melody valve implantation was attempted; otherwise, the conduit was considered anatomically unsuitable, and no implantation was attempted. Post-dilation of the valve was permitted at the discretion of the operator.

Additional interventional procedures during the same catheterization procedure, including stenting of the conduit with a bare-metal stent, were not permitted. The original protocol was, however, amended after the first 34 patients to allow concomitant transcatheter interventions at the time of Melody valve implantation at the discretion of the investigator.

Concomitant Medications:

All patients received heparin to maintain an activated clotting time >250 seconds during the procedure. Antibiotic prophylaxis was given before and after the procedure.

Principal Findings:

A total of 136 patients were enrolled in this cohort between January 2007 and August 2009. The major original cardiac diagnoses were tetralogy of Fallot (48%), aortic valve disease after a Ross procedure (28%), transposition of the great arteries (11%), and truncus arteriosus (10%). The primary implantation indication among catheterized patients was PR in 52%, RVOT obstruction in 26%, and mixed disease in 22%. About 76% had a homograft conduit, and 19% had a bioprosthetic valve or conduit. The majority of patients had New York Heart Association (NYHA) class II (67%) or III (16%) symptoms. The median RV systolic pressure was 74 mm Hg (noninvasive)/65 mm Hg (on catheterization), with a median RVOT gradient of 34.7 mm Hg (noninvasive)/37 mm Hg (on catheterization). The median pulmonary artery systolic pressure on catheterization was 28.5 mm Hg. In patients who received magnetic resonance imaging (MRI), the median RV ejection fraction was 42.8%, with a median RV end-diastolic volume of 188 ml.

Transpulmonary valve (TPV) placement was attempted in 124 of the 136 enrolled patients, mainly through the femoral route (120 patients). The angiographic conduit diameter prior to intervention ranged from 5-19.7 mm (median 12.9 mm), and the diameter of the sizing balloon waist (measured after predilation, when performed) ranged from 14-20 mm (median 17 mm). Acutely, TPV placement resulted in acute reduction in the RV pressure to a median of 41.5 mm Hg, the peak RVOT pressure gradient to a median of 12 mm Hg, and the ratio of RV to aortic pressure to a median of 0.42. Only one patient was noted to have moderate angiographic PR immediately post-procedure. Serious adverse events (6%) included coronary artery dissection, conduit rupture needing emergent surgery, contained conduit rupture/tear, femoral vein thrombosis, and guidewire-induced perforations of a distal pulmonary branch. The patient with coronary dissection subsequently expired. The other seven patients with complications were discharged within 1 week of implantation, whereas all other patients were discharged from the hospital the day of or the day after the TPV implantation.

There were no additional deaths over the duration of follow-up. On echocardiographic follow-up 6 months after TPV implantation, the median RV pressure had decreased from 74.0 to 51.0 mm Hg (p = 0.001), and the mean RVOT gradient had decreased from 34.3 to 17.5 mm Hg (p = 0.001). Similarly, on MRI, the median RV end-diastolic volume had decreased from 173 to 152 ml (p = 0.001), and the median PR fraction had decreased from 26.7% to 1.8% (p = 0.001). The median RV ejection fraction was, however, unchanged (43.8% vs. 41.5%, p = 0.9). On cardiopulmonary testing, the peak relative VO2 was similar pre- and post-TPV implantation (25.0 vs. 24.9 ml/kg/min, p = 0.44). The majority of patients experienced some improvement in NYHA class.

Stent fractures were noted in 25 patients, with only one being classified as major (multiple strut fractures with a loss of stent integrity) on initial evaluation. In addition, six progressed from minor to major during the course of follow-up. Freedom from diagnosis of stent fracture was 83.7% at 7.5 months and 77.8% at 14 months. Eleven patients underwent RVOT reintervention after TPV, including nine who received a second Melody valve. Freedom from TPV dysfunction (moderate or greater PR, mean Doppler RVOT gradient ≥40 mm Hg, or reintervention) was 93.5% at 1 year and 85.6% at 2 years. On multivariate analysis, higher mean RVOT gradient on discharge echocardiogram and younger age were associated with shorter freedom from TPV dysfunction.

Interpretation:

The results of this expanded cohort of 136 patients referred for Melody TPV implantation indicate that it is safe and efficacious in patients with RVOT obstruction and/or severe PR. Successful TPV implantation was associated with a significant improvement in hemodynamic, anatomic, and functional parameters at 6 months.

Serious adverse effects were about 8%, with one fatality. Stent fracture was relatively common (18%), with a freedom from stent fracture rate of about 80% at 14 months. Reinterventions were required in 11 patients, all due to RVOT obstruction. This highlights the importance of appropriate patient selection, adequate relief of obstruction at the time of Melody valve placement, and measures to prevent or manage stent fracture. These findings are exciting, but additional data and longer follow-up are necessary.

References:

McElhinney DB, Hellenbrand WE, Zahn EM, et al. Short- and medium-term outcomes after transcatheter pulmonary valve placement in the expanded multicenter US Melody valve trial. Circulation 2010;122:507-16.

Keywords: Tetralogy of Fallot, Follow-Up Studies, Multivariate Analysis, Arterial Pressure, Allografts, Femoral Vein, Truncus Arteriosus, Magnetic Resonance Imaging, Stents, Patient Selection, Mitral Valve Prolapse, Thrombosis, Pulmonary Valve Insufficiency, Catheterization, Myxoma


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