|Home | About | Journals | Submit | Contact Us | Français|
The purpose of this study was to demonstrate the feasibility of percutaneous transvenous mitral valve-in-ring (VIR) implantation using the Melody® valve in an ovine model.
The recurrence of mitral regurgitation (MR) following surgical mitral valve (MV) repair in both adult and pediatric patients remains a significant clinical problem. Mitral annuloplasty rings are commonly used in MV repair procedures and may serve as secure landing zones for percutaneous valves.
Five sheep underwent surgical MV annuloplasty (24mm, n=2; 26mm, n=2; 28mm, n=1). Animals underwent cardiac catheterization with valve-in-ring implantation via a trans-femoral venous, trans-atrial septal approach 1 week following surgery. Hemodynamic, angiographic, and echocardiographic data were recorded before and after VIR.
VIR was technically successful and required less than 1 hour of procedure time in all animals. Fluoroscopy demonstrated securely positioned Melody® valves within the annuloplasty ring in all animals. Angiography revealed no significant MV regurgitation in 4, and moderate central MV regurgitation in the animal with the 28mm annuloplasty. All animals demonstrated vigorous LV function, no outflow tract obstruction, and no aortic valve insufficiency. There were no differences in the hemodynamic measures following valve implantation.
This study demonstrates the feasibility of a purely percutaneous approach to MV replacement in patients with preexisting annuloplasty rings. This novel approach may be of particular benefit to patients with failed repair of ischemic MR, and in pediatric patients with complex structural heart disease.
Mitral valve repair with annuloplasty device is the preferred surgical therapy for mitral regurgitation (MR)(1). Recent studies have called into question the durability of mitral valve repair for functional, degenerative and congenital etiologies(1–3).
The recurrence rate of significant MR after undersized annuloplasty for ischemic mitral regurgitation (IMR) approaches 30% six months after surgery. Recent studies have documented the development of recurrent MR after repair for degenerative etiologies to be 2 to 4% per year. Due to very complex pathologies, recurrence of regurgitation following valve repair for congenital anomalies is also common(4).
Recently, the development of novel valve technologies has made the percutaneous replacement of the aortic and pulmonary valves possible(5–7). However, percutaneous replacement of the mitral valve (MV) is not currently possible due to inherent anatomic features of the MV that make fixation and perivalvular seal with currently available devices a challenge. Recent clinical reports and animals studies have demonstrated that the presence of a surgically placed annuloplasty device or a bioprosthetic valve makes MV replacement with valved-stents feasible. This technique has been termed the valve-in-ring (VIR) or valve-in-valve (VIV) procedure and has been performed surgically, via transatrial(8) and transapical(9–11) approaches using the Sapien® Transcatheter Heart Valve (Edwards Lifesciences, Irvine, California). Given the growing awareness of the limitations of valve repair durability, VIR offers a potential remedial procedure for high-risk adult and pediatric patients who develop recurrent MR after MV repair. In this study we report on the feasibility of performing VIR via a completely percutaneous approach using the Melody® transcatheter valve (Medtronic, Minneapolis, MN) in a sheep model of mitral valve repair.
Five sheep had surgical MV annuloplasty with CE -PhysioTM devices (24mm [N=2]; 26mm [N=2]; 28mm [N=1]; Edwards Lifesciences, Irvine, California) using standard techniques.
One week following surgery, animals were brought to the catheterization laboratory for the Melody VIR procedure. Vascular access was obtained in the usual fashion. Under intracardiac echocardiographic (ICE) guidance, an atrial septal defect (ASD) was created. Next, a pre-shaped, super-stiff 0.035” guidewire (Lunderquist® wire, Cook Medical, Bloomington, IN) was introduced and looped in the LV apex (Figure 1A–B), creating a railway from the iliac vein to the LV via the ASD.
Melody valves were crimped onto 22 mm diameter angioplasty balloons (22mm x 4 cm BIB balloon Catheter, NuMed Inc. Hopington NY). The crimped Melody valve was advanced over the wire, through the 22Fr sheath and centered within the annuloplasty ring. Once in position, the device was deployed via standard balloon inflation technique (Figure 1B). Following deployment, the small ASD was device-closed (Helex®, Gore Medical). Post deployment angiography was performed to assess valve position and function. Follow up hemodynamics and echocardiography were recorded and compared to baseline values. Procedure time, defined as beginning after vascular access was established, and ending with ASD closure, was recorded for all animals. After a period of observation (6 hours), animals were euthanized. Necroscopy was performed including gross inspection of the valve-in-ring complex. All experiments were approved by the University of Pennsylvania’s animal use committee.
Hemodynamic measurements before and after VIR were summarized using standard descriptive statistics and reported as mean ± standard deviation. Comparisons were made using paired students t-test. Statistical significance was defined as a P value ≤ 0.05.
All animals underwent successful surgical placement of an annuloplasty device.
The only significant difference between the pre and post VIR hemodynamic measures was an increased systolic (and mean) pulmonary artery pressure (33.8 + 3.7 vs. 38 + 4.8; p=0.008) and a trend towards increased cardiac output (4.1 + 0.4 vs. 5.2 + 0.9; p=0.06) . Otherwise no significant differences were noted as shown in Table 1. The greater and lesser diameters of the “D-shaped” rings (Figure 2) were recorded for all animals and are listed in Table 2. All VIR procedures were successful, and each required less than 1 hour of procedure time (Table 2). Though engineered to be circular upon full deployment, the Melody device conformed to the “D-shaped” annuloplasty ring in all cases (Figures 2 & 5). Despite this conformational change, the valves functioned well in the 24 and 26mm rings. Follow-up angiography and echocardiography revealed excellent left ventricular systolic function. There was mitral regurgitation through a central coaptation defect in 3 animals: trivial-to-mild in 2 and moderate-to-severe in one (Figure 3). In this animal, the 28mm annuloplasty ring appeared too large for secure anchoring of the Melody device when it was expanded to 22 mm. Therefore, this valve was expanded beyond the listed maximum diameter to approximately 24mm, resulting in malcoaptation of the valve leaflets and moderate-to-severe central MR . There was no LV outflow tract obstruction (LVOTO), aortic insufficiency or perivalvular regurgitation in any animal (Table 1 and Figure 4).
Following euthanasia, necropsy demonstrated that all Melody valves were anchored securely within the annuloplasty with a tight seal formed between the Melody device and the ring circumferentially (Figure 5).
In this report we describe the first transvenous, transatrial septal VIR implantation using the Melody device. Via standard vascular access and transseptal techniques, we successfully deployed the Melody valve into the mitral position from the venous circulation in all animals, without difficulty or complication. The Melody valves were securely seated in all cases. Importantly, although there was a conformational change noted in the Melody valves from “round” to “oval” or “D-shaped” when implanted into the annuloplasty rings, there was no perivalvular leakage noted, and not greater than trivial to mild central MR except in the one animal in which we intentionally oversized the device (Figure 4). The only significant hemodynamic change noted following VIR was an increase in PA pressure (p=0.008). The exact cause of this difference is unclear, however it was likely due to a trend towards increased cardiac output secondary to sympathetic upregulation (p=0.06) post-VIR. Theoretically, increased PA pressure could also be secondary to pulmonary vein obstruction or to an increase in LA pressure caused by MR and/or MS. However, the pulmonary veins were unobstructed, and the mean LA pressure did not increased following VIR (p=0.55). The success and relative ease of this procedure highlights the potential for this approach in patients with ongoing MV dysfunction despite prior surgical repair.
Irrespective of the cause, surgical repair of systemic atrioventricular (AV) valve regurgitation (mitral, common AV, or tricuspid valves) carries a significant risk for recurrence in both adult and pediatric patients(4,12). Despite this risk, in most circumstances, valve repair is still preferred over replacement; due to durability concerns associated with tissue valves and to the reduced need for systemic anticoagulation when compared to mechanical valves(13). In the last decade, the advent of percutaneous valve replacement has resulted in new minimally invasive therapeutic options for patients with dysfunctional aortic and pulmonary valves(5–7). While many promising percutaneous mitral valve (MV) repair technologies have been developed (2,14), percutaneous MV replacement with a single device remains elusive. The inherent anatomic features of the MV make fixation and perivalvular seal a troublesome challenge. In particular the mitral annulus lacks a uniform “landing zone” for secure deployment of a percutaneous device. Despite these challenges, promising steps towards one-stage percutaneous MV replacement are being made (15,16). In the meantime, minimally invasive surgical MV replacement via valve-in-valve (VIV) and more recently valve-in-ring (VIR) procedures have been described in which the Edwards Sapien device was deployed into previously placed bioprosthetic tissue valves(9,10) and/or annuloplasty rings(8,11) via a surgical transapical or transatrial approach. These procedures are intended to extend the functional life of the surgical valve procedure in a manner analogous to Melody and Sapien valve treatment for dysfunctional surgical conduits in the pulmonary position. The VIR and VIV procedures have the potential to change the way that MV patients are managed, especially as percutaneous valve technologies undergo further refinements that optimize their performance in these new settings.
The Melody valves used in this experiment were previously handled and cosmetically flawed, thus not viable for commercial use and not optimal for functionality testing. Furthermore, these devices are engineered for implantation into the pulmonary circulation. They are undersized relative to the normal adult mitral annulus (max functional diameter = 22mm), and not intended for use in the systemic circulation, where the afterload is generally much higher. Despite these limitations, these results were a proof of concept sufficient to demonstrate the feasibility of the transvenous VIR procedure.
This work was supported in part by HL-63954 and HL-73021 from the National Institutes of Health, Bethesda, MD.
There are no relevant relationships with industry to disclose.
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.