Author + information
- Received November 25, 2014
- Revision received December 29, 2014
- Accepted January 14, 2015
- Published online March 31, 2015.
- Joachim Schofer, MD∗,
- Klaudija Bijuklic, MD∗,
- Claudia Tiburtius, MD∗,
- Lorenz Hansen, MD∗,
- Adam Groothuis, PhD† and
- Rebecca T. Hahn, MD‡∗ ()
- ∗Hamburg Universitary Cardiovascular Center, Hamburg, Germany
- †Mitralign, Inc., Tewksbury, Massachusetts
- ‡Columbia University Medical Center/New York Presbyterian Hospital and the Cardiovascular Research Foundation, New York, New York
- ↵∗Reprint requests and correspondence:
Dr. Rebecca T. Hahn, Columbia University Medical Center, New York-Presbyterian Hospital, 177 Fort Washington Avenue, New York, New York 10032.
Background Severe tricuspid regurgitation is associated with poor prognosis; however, there are limited Class I indications for intervention, and high–surgical risk patients may go untreated. We report the first-in-human successful transcatheter tricuspid valve repair for severe tricuspid regurgitation.
Objectives The objective of this study was to show the feasibility of a transcatheter tricuspid annular repair.
Methods Compassionate-use approval for the procedure was obtained from the regulatory organization in Germany. To perform the transcatheter bicuspidization of the tricuspid valve, the Mitralign system was used to place pledgeted sutures by means of a trans-jugular venous approach. Insulated radiofrequency wires were positioned 2 to 5 mm from the base of the posterior leaflet, 2.6 cm apart. The sutures were drawn together and locked, plicating the posterior annulus.
Results Reconstruction of the 3-dimensional transesophageal echocardiographic dataset at baseline revealed a tricuspid valve annular area of 14.1 cm2, and effective regurgitant orifice area was 1.35 cm2. There was a significant reduction in annular area (57%) and effective regurgitant orifice area (53%) measured with 3-dimensional transesophageal echocardiography, at 6.05 cm2 and 0.63 cm2, respectively. Hemodynamic parameters also improved with a reduction in right atrial pressure from 22 mm Hg at baseline, to 9 mm Hg and an increase in left ventricular stroke volume from 42 ml at baseline to 72 ml.
Conclusions Transcatheter tricuspid valve repair could become an effective treatment for high–surgical risk patients who are non-responsive to optimal medical therapy.
A growing number of studies suggest that severe tricuspid regurgitation (TR) is associated with poor prognosis (1–7). Class I indication for TR repair is currently limited to patients with concomitant mitral valve disease requiring surgery (Level of Evidence: B) (8). Multiple surgical repair procedures have been proposed, including the Kay bicuspidization procedure (9), in which the annulus is plicated along its muscular part adjacent to the posterior leaflet. This repair method has shown good mid-term (10) and long-term (11) results. Percutaneous technologies to repair secondary TR represent a potential tool to treat patients at high risk for open heart surgery. Herein we report the first successful case of a direct transcatheter tricuspid repair (TTVR) for severe TR.
An 89-year-old woman presented with recurrent right heart decompensation manifesting as severe edema of the lower extremities with skin ulcerations, stage III/IV chronic kidney disease (creatinine = 1.85 ml/dl, glomerular filtration rate = 27 ml/min), and chronic atrial fibrillation. Echocardiography showed preserved left ventricular (LV) size and function (ejection fraction, 55%) with reduced forward stroke volume (42 ml); mild to moderate mitral and aortic regurgitation; severe dilation of the right atrium and ventricle with slightly impaired right ventricular function; and severe TR with tethered, non-thickened leaflets. Right heart catheterization revealed a right atrial pressure of 22 mm Hg and pulmonary artery systolic pressure of 40 mm Hg. The echocardiographic and hemodynamic findings are consistent with “isolated tricuspid regurgitation” (7). The patient’s Log EuroSCORE (European System for Cardiac Operative Risk Evaluation) was 28%, and surgical intervention was deemed too high-risk; she agreed to undergo a transcatheter bicuspidization of her tricuspid valve. Because there are no currently accepted indications for intervention in the absence of concomitant mitral valve disease, we approached the regulatory organization in Germany (Bundesinstitut für Arzneimittel und Medizinprodukte), which approved compassionate use of the Mitralign system (Mitralign Inc., Tewksbury, Massachusetts) to plicate the tricuspid annulus.
With the patient under general anesthesia, 2- and 3-dimensional (2D and 3D) transesophageal echocardiography (TEE) was performed at baseline, during and after the procedure. To perform the transcatheter bicuspidization of the tricuspid valve, we used the Mitralign system to place pledgeted sutures by means of a trans-jugular venous approach. Over a standard angiographic wire, we introduced an articulating 8-F wire delivery catheter in a retrograde fashion across the tricuspid. The retrograde approach allows for better control and accuracy of placement of the wires into the annulus while TEE guidance is used. An 8-F deflectable catheter was advanced across the tricuspid valve and positioned into the right ventricle by means of echocardiographic guidance. Once introduced into the right ventricle, the catheter was articulated under the annulus to either the postero-anterior commissure or the septo-posterior commissure. Once the anatomic site was confirmed on fluoroscopy and TEE, an insulated radiofrequency wire was advanced and positioned 2 to 5 mm from the base of the leaflet and within the annulus, directed toward the right atrium to avoid right coronary artery perforation (Figure 1). Once the wire was through the annulus, a pledget delivery catheter was advanced over the wire from the right atrium across the annulus to the right ventricle. The wire was removed, and half the pledget was delivered and cinched in the sub-annular region of the ventricle. On withdrawal of the pledget delivery catheter from the ventricle, the remaining pledget was extruded and cinched on the atrial surface of the tricuspid annulus. The end result was a suture supported on both the ventricular and atrial sides of the annulus with folded pledgets (Figure 2). The steps were then repeated on the opposite anatomic site of the posterior commissure. A dedicated plication lock device was used to bring the 2 pledgeted sutures together, plicating the annulus and effectively bicuspidizing the tricuspid valve (Figure 3).
Reconstruction of the 3D TEE dataset at baseline revealed a tricuspid valve annular area of 14.1 cm2 and effective regurgitant orifice area (EROA) of 1.35 cm2 (Figure 4). There was a significant reduction in annular area (57%) and EROA (53%) measured with 3D TEE, at 6.05 cm2 and 0.63 cm2, respectively. Hemodynamic parameters also improved, with a reduction in right atrial pressure from 22 mm Hg at baseline to 9 mm Hg and an increase in LV stroke volume from 42 ml at baseline to 72 ml. The patient tolerated the procedure well, was extubated the same day, and was discharged 5 days after the procedure. Since discharge, the patient has continued to require her usual aggressive medical management; however, she subjectively feels better, her edema has lessened, and her renal function has significantly improved (creatinine = 1.0 ml/dl, glomerular filtration rate = 55 ml/min).
Functional or secondary TR is the most common etiology of severe TR in the Western world (12). Interest in the tricuspid valve has increased in recent years (13–15) with the recognition of the impact of secondary tricuspid regurgitation on outcomes (1,2,5,7,16,17) and the benefits of tricuspid repair (6,18). TR is an independent predictor of long-term mortality (2,7). The prevalence of secondary TR with mitral valve disease is >30% (13,14), with some studies suggesting that more than 1.6 million patients in the United States may have this disease (19).
Outcomes related to isolated tricuspid regurgitation—similar to our case—were recently studied by Topilsky et al. (7). These authors defined isolated TR as requiring the following: 1) TR holosystolic and functional; 2) no probable pulmonary hypertension (<50 mm Hg); 3) no overt TR cause (no intrinsic tricuspid disease, LV ejection fraction ≥50%, no pacemaker/defibrillator wire across the tricuspid, no other valve disease more than mild, no disease that may cause TR, no congenital or pericardial heart disease); and 4) no previous valve surgery. Patients with isolated, severe TR had a significantly reduced 10-year survival compared with patients with less significant disease. In this study, both the qualitative multi-window, multi-parameter method (adjusted hazard ratio [HR]: 1.78; 95% confidence interval [CI]: 1.10 to 2.82; p = 0.02) and proximal isovelocity surface area quantitative EROA ≥40 mm2 (adjusted HR: 2.67; 95% CI: 1.66 to 4.23; p < 0.0001) independently predicted higher mortality rates. Adverse outcomes with EROA ≥40 mm2 were seen, independent of all other characteristics, such as right ventricular size or function, comorbidity, or pulmonary pressure (p < 0.0001 for all).
Currently, TR is treated primarily with optimal medical therapy or surgery (20). In patients who have development of severe TR late after left heart valve surgery, operative mortality rate may be as high as 10% to 20% (13,21–23). In patients who have failed initial surgical repair of the tricuspid valve, transcatheter placement of balloon-expandable valves (valve-in-ring) have been successfully performed (24). In addition, indirect transcatheter procedures have been reported for the treatment of severe, symptomatic secondary tricuspid regurgitation. These techniques focus on reducing the regurgitant flow into the vena cava by the implantation of transcatheter valves in these large vessels (25,26). This solution, however, fails to treat the primary disease process of the tricuspid valve, although Laule et al. (26) reported remodeling of the right heart.
This first-in-human report of a direct TTVR approach shows the feasibility and safety of this procedure as well as a significant reduction in annular area and EROA, resulting in a marked reduction in TR (Central Illustration). As a consequence, right atrial pressure and LV stroke volume showed marked improvement. Anatomic imaging with the use of 2D and 3D TEE was integral to the success of the procedure. The new comprehensive TEE guideline, published by the American Society of Echocardiography (27), describes advanced imaging views for the tricuspid valve. The use of 3D technology, whether simultaneous multiplane imaging or full-volume acquisitions (28), allows for the precise placement of catheters and wires. Both 2D and 3D TEE were essential adjuncts to fluoroscopic imaging for precise positioning of the pledgeted sutures in the annulus, as well as for avoidance of complications such as coronary or chamber perforation. Thus, TEE imaging was integral to the success of the current procedure.
This is a single case report showing feasibility and reduction in annular dimensions for isolated TR. The durability and long-term effect of TTVR, as well as the efficacy for other etiologies of TR, should be studied in larger trials.
This case provides a proof of principle that a direct TTVR for severe TR could become an effective treatment for high–surgical risk patients who are non-responsive to optimal medical therapy. Larger numbers of patients are needed to assess the feasibility and efficacy of this treatment.
COMPETENCY IN MEDICAL KNOWLEDGE: The Mitralign device, designed to plicate the annulus of the mitral valve, may be applicable to the tricuspid valve as well.
TRANSLATIONAL OUTLOOK: Additional experience with this percutaneous, transesophageal, echocardiographically guided procedure to reduce the diameter of the valve annulus and lessen tricuspid regurgitation is needed to better define its role in patients with severe primary or secondary tricuspid regurgitation. Assessment of the effect of the procedure on symptoms, right heart remodeling, and clinical outcomes requires clinical trials involving additional patients.
Mitralign provided devices and training support for device use. Dr. Groothuis is a paid employee of Mitralign, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- effective regurgitant orifice area
- left ventricular
- transesophageal echocardiogram
- tricuspid regurgitation
- transcatheter tricuspid valve repair
- Received November 25, 2014.
- Revision received December 29, 2014.
- Accepted January 14, 2015.
- 2015 American College of Cardiology Foundation
- Nath J.,
- Foster E.,
- Heidenreich P.A.
- Hung J.,
- Koelling T.,
- Semigran M.J.,
- et al.
- Topilsky Y.,
- Nkomo V.T.,
- Vatury O.,
- et al.
- Nishimura R.A.,
- Otto C.M.,
- Bonow R.O.,
- et al.
- Taramasso M.,
- Vanermen H.,
- Maisano F.,
- et al.
- Antunes M.J.,
- Barlow J.B.
- Rogers J.H.,
- Bolling S.F.
- Voelkel N.F.,
- Quaife R.A.,
- Leinwand L.A.,
- et al.
- ↵(1992) Complications and mortality of percutaneous balloon mitral commissurotomy. A report from the National Heart, Lung, and Blood Institute Balloon Valvuloplasty Registry. Circulation 85:2014–2024.
- Nishimura R.A.,
- Otto C.M.,
- Bonow R.O.,
- et al.
- Laule M.,
- Stangl V.,
- Sanad W.,
- et al.
- Hahn R.T.,
- Abraham T.,
- Adams M.S.,
- et al.