Abstract: Background. This study sought to describe a single center’s experience with transcatheter mitral valve-in-valve (TM-ViV) implantation. Methods. Consecutive patients who had TM-ViV due to degenerative biological valve prosthesis at a single center during a 4-year period were identified from a prospectively maintained database. Operative outcomes were assessed both in-hospital and at 30 days. The primary outcome was in-hospital mortality. Secondary outcomes included valve function, functional status, and quality of life at follow-up. Results. Mean (± standard deviation) patient age was 69 ± 12 years and all patients were high risk for redo surgery (STS risk score, 9.6 ± 6.2%). The primary mechanism of bioprosthetic valve failure was stenosis in 7 patients (47%) and regurgitation in 8 patients (53%). Mean duration between mitral valve replacement (MVR) and transcatheter MVR was 89 months (range, 66-72 months). Failed bioprosthetic valves were replaced with Sapien XT (n = 10; 67%), Sapien (n = 4; 26%), or Sapien S3 valves (n = 1; 7%) (all valves manufactured by Edwards Lifesciences). Procedural success was 100%. No intraoperative deaths were recorded. Postimplantation valve hemodynamics was satisfactory, with a significant improvement in mean valvular gradient (∆ = -12 mm Hg; P<.001) and mitral valve area (∆ = 0.9 cm2; P<.01). At 30-day follow-up, no reports of death, disabling stroke, or rehospitalization for cardiac reasons was recorded. Health status scores were available for 11 of the 15 study patients (73%). Except for 1 patient, significant improvements were seen for all components of the health assessment survey. Conclusions. TM-ViV for failing biological mitral prosthesis can be performed with minimal operative morbidity and acceptable mid-term clinical and hemodynamic outcomes.
J INVASIVE CARDIOL 2020;32(2):49-54. Epub 2019 November 15.
Key words: bioprosthesis, valve-in-valve replacement
Over the past two decades, the use of bioprosthetic valves for valvular pathologies has grown steadily, thus leading to many patients requiring redo surgery as a result of deteriorating valves. Among older patients with multiple comorbidities, redo cardiac surgery is associated with a significantly higher mortality and morbidity especially for mitral valve surgery considering the complexity of the procedure.1
Transcatheter valve-in-valve has emerged as a clinically effective option in these patients deemed ineligible for redo surgery.2 Multiple implantation techniques are being developed and are still under rigorous scrutiny for the widespread clinical application of this technology. Transcatheter mitral valve-in-valve (TM-ViV) implantation into failed mitral bioprostheses was first reported by Cheung et al in 2009.3 Since then, there have been several reports investigating its safety and efficacy, and different approaches (transapical transseptal, transatrial) have been attempted.4-6 Clearly, the clinical impact of this new technology can be anticipated as the proportion of failing mitral bioprosthetic valves continue to rise. Certainly, with the current high-risk aging population, a less-invasive approach for mitral valve replacement (MVR) will be desirable.
Herein, we report on our experience with 15 consecutive patients with symptomatic mitral biological valve dysfunction managed successfully by TM-ViV using Sapien-type balloon-expandable valves (Edwards Lifesciences) via multiple approaches.
Patients who underwent TM-ViV replacement due to degenerative biological valve prosthesis at a single center during a 4-year period were identified from a prospectively maintained database. Indications for reoperative MVR were according to the American College of Cardiology/American Heart Association guidelines for mitral valve surgery.7 All patients had a previous MVR, and were evaluated by a multidisciplinary heart team that consisted of at least two cardiac surgeons and an interventional cardiologist and were considered high risk for reoperative surgical MVR.
Multiple imaging modalities (transthoracic echocardiography, three-dimensional transesophageal echocardiography [TEE] and multislice computed tomography [CT] angiography) were used to confirm bioprosthetic valve diameters and for valve sizing and positioning. A well-written informed consent was obtained from all study participants, and the study was approved by the institutional review board of the Newark Beth Israel Medical Center.
Data pertaining to patient demographics, clinical characteristics at baseline, procedural details, and postoperative outcomes were reviewed. Postoperative follow-up exams were performed at a dedicated transcatheter aortic valve replacement (TAVR) clinic according to institutional protocols (at 2 weeks, 1 month, 6 months, 1 year and annually post procedure). Follow-up included clinical evaluation and transthoracic echocardiographic imaging to evaluate valve function. Mortality was assessed by using data from in-hospital records in combination with records from the Social Security Death Index database. Procedural success and complications were reported according to the Valve Academic Research Consortium (VARC)-2 definitions.8 Health status assessment was evaluated preoperatively for all patients. The 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12) was used in evaluating disease-specific health status. The validated KCCQ-12 quantifies symptom frequency, physical and social limitations, and quality of life impairment due to heart failure, into separate domain scores as well as an overall summary score (KCCQ-OS). The KCCQ-OS correlates with the New York Heart Association (NYHA) functional class as follows: class I = KCCQ-OS 75-100; class II = KCCQ-OS 60-74; class III = KCCQ-OS 45-59; and class IV = KCCQ-OS 0-44. Changes in KCCQ-OS of 5, 10, and 20 points are consistent with small, moderate, or substantial clinical improvements, respectively.9,10
Procedure. All cases were performed in the hybrid operating room equipped with standby cardiopulmonary bypass under general anesthesia. Twelve of the cases were performed via a transapical approach, 2 through a median sternotomy, and 1 through a transseptal approach. Sapien balloon-expandable valves (Edwards Lifesciences) were used in all cases. An appropriately sized Sapien valve was chosen based on the internal diameter (ID) of the pre-existing biological mitral prosthesis as reported by the manufacturer and by using a combination of TEE and CT angiography. Implantation and valvular performance were performed and assessed under TEE guidance (Figure 1).
Statistical analysis. Continuous variables are summarized as mean ± standard deviation and categorical variables as numbers and percentages. All analyses were performed with JMP, version 10 (SAS). P-values <.05 were considered statistically significant.
Between July 2013 and September 2016, a total of 15 patients had transcatheter MVR for failed bioprosthetic mitral valves. Baseline demographics and clinical characteristics of the study population are given in Table 1. Mean patient age was 69 ± 12 years. The study population consisted of 13 women and 2 men. Twelve patients had NYHA class III/IV heart failure symptoms and mean Society of Thoracic Surgeons (STS) mortality risk score of all patients was 9.6 ± 6.2. Common comorbidities included coronary artery disease, chronic atrial fibrillation, chronic obstructive lung disease, and pulmonary hypertension. Eleven patients (73%) had a history of moderate-severe pulmonary hypertension.
The primary mechanism of bioprosthetic valve failure was stenosis in 7 patients (47%) and regurgitation in 8 patients (53%). Eight (53%) of the mitral bioprostheses replaced were Carpentier-Edwards Perimount devices (Edwards Lifesciences). Mean duration between MVR and transcatheter MVR was 89 months (range, 66-72 months). Measured IDs of failed bioprostheses ranged from 20.3-26.0 mm. Failed bioprosthetic valves were replaced with Sapien XT (n = 10; 67%), Sapien (n = 4; 26%), and Sapien S3 valves (n = 1; 7%) (Edwards Lifesciences). Further details of mitral valve characteristics are given in Table 2.
Operative outcomes. Procedural success was 100%, with no cases of valve malpositioning or embolization. A second valve was required for 1 patient who developed severe paravalvular leak post implantation. Except for the 2 patients who had the procedure via a median sternotomy approach, cardiopulmonary bypass was not required in the remaining 12 cases.
Postimplantation valve hemodynamics were satisfactory with a significant improvement in mean valvular gradient (Δ = -12 mm Hg; P<.001) and mitral valve area (Δ = 0.9 cm2; P<.01). An absolute increase in left ventricular ejection fraction was also noted. No case of mitral regurgitation was found post implant (Figure 2).
The mean duration of hospital stay was 9 ± 5 days. Incidence of postoperative complications was 13% (n = 2) and this included acute kidney injury in 1 patient and respiratory failure in 1 patient. A permanent pacemaker was required in 1 patient and severe paravalvular regurgitation post implantation was seen in another patient. No intraoperative deaths were recorded (Table 3).
At 30-day follow-up, no reports of death, disabling stroke, or rehospitalization for cardiac reasons was recorded. All patients had NYHA functional status I/II and valve performance was still satisfactory. Mean valvular gradient, mitral valve area, and left ventricular ejection fraction did not change significantly at 30 days when compared with postimplant values. No degree of mitral regurgitation remained in any patient at 30 days (Figure 3).
Health status scores were available for 11 patients (73%). Of these, 6 patients had both pre- and postoperative 30-day health assessment scores, 4 had only postoperative assessment scores, and 1 had only preoperative assessment scores. Variations in change of KCCQ scores at 30-day follow-up are illustrated in Figure 4. Except for 1 patient, significant improvements were seen for all components of the health assessment survey. The 4 patients who had postoperative KCCQ scores but no preoperative scores reported scores that were higher than the mean preoperative scores recorded for all patients.
Mortality rate at 1 year post procedure was 27% (n = 4). Two of the remaining 11 patients were NYHA class III and no patients were NYHA class IV functional status.
In the present study, we demonstrated the safety and efficacy of TM-ViV in patients with degenerated mitral valves either due to mitral regurgitation (53%) or mitral stenosis (47%). Procedural outcomes were congruent with previous studies and demonstrated a 100% success rate with no evidence of valve malposition or embolization. Postimplantation and 30-day outcomes also demonstrated a 0% mortality rate. The success of the procedure was mainly quantified with three parameters: change in valve function; change in NYHA class; and quality of life. The patients demonstrated a significant increase in effective orifice area (EOA) and a significant decrease in mitral valve gradient (MVG) at day 0 and day 30 when compared to preimplantation measurements. At the time of the procedure, most patients (80%) who presented with NYHA III/VI functional status showed significant improvement at day 30 and these changes persisted at 1-year follow-up, with almost every patient classified as NYHA I/II. Moreover, 60% of the patients who had severe or moderate mitral valve regurgitation prior to the implantation and degree of mitral regurgitation had significantly resolved after the procedure.
The overall quality of life improved for 14 of the 15 patients, as evidenced by the increases in each component of the KCCQ health assessment of social limitation, quality of life, symptoms, and physical limitations. On postimplantation day 30, fourteen of the 15 patients had improvements in each survey category: overall summary score (Δ = 13), social limitations (Δ = 23), quality of life (Δ = 18), symptoms (Δ=14), and physical limitations (Δ = -1). Although these results aren’t as impressive as results from TAVR and edge-to-edge transcatheter MVR studies performed by Arnold et al,9,11 the data are robust and conclusive. The differences in KCCQ-OS scores are most likely attributed to the variations in the particular procedures and in the health status of the patient population, which has been shown to be an independent risk factor for less health status recovery.11 Regardless, we show similar positive trends, which are appreciated with increasing KCCQ-OS scores.
In-hospital and 30-day mortality rates are strong indicators of surgical and technical success, so by achieving in-hospital and 30-day mortality rates of 0%, our study demonstrates the feasibility and efficacy of TM-ViV in high-risk patients. These statistics are congruent with previous studies that reported 1 death at 30 days post implantation due to cannulation-related apical bleeding; each study reported a procedural success rate of 100% as well as a 30-day mortality rate of 0%.1-5 Our patient population of predominantly elderly females with multiple comorbidities was also similar to these studies.
Significant improvements in valve function as assessed by the EOA and MG were noted in all patients. Post implant, the MGs decreased from 11.6 mm Hg to 5 mm Hg; these changes even persisted at 30-day follow-up. In a similar fashion, the mean EOA increased from 1.1 cm to 2 cm post implant and at 30 days. These results are similar to previous studies.1-5
As expected, these findings translated into better patient functional status at follow-up. Our 1-year mid-term postimplantation outcomes demonstrated similarly successful results in 9 of the 11 patients who survived to 1 year, while 2 patients progressed to NYHA class III (13%). The slight variations in the valve function of our patients and patients from other studies is most likely due to variations in patients and differences in assessing valve size.
Study limitations. As with previous TM-ViV studies, we present a small (15 patient), single-institution retrograde analysis without comparison with surgical management. Even though it is one of the largest TM-ViV cohorts reported to date, our cohort is female-dominant and is specific to an urban demographic, where patients tend to have fewer comorbidities. Therefore, in certain instances, our results may not be appropriately extrapolated to other populations. Larger studies will facilitate greater risk stratification and elucidate more-detailed indications for TM-ViV in high-risk patients.
We have demonstrated that TM-ViV replacement is an acceptable treatment in select high-risk patients with degenerated bioprostheses. Our study showed successful mitral implantation in patients with degenerated bioprostheses and reported excellent valvular hemodynamics and clinical outcomes. This study, therefore, supports other studies on TMViV as an alternative to conventional redo surgery in certain high-risk patients.
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8. Kappetein AP, Head SJ, Genereux P, et al. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document (VARC-2). Eur J Cardiothorac Surg. 2012;42:S45-S60.
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11. Arnold SV, Li Z, Vemulapalli S, et al. Association of transcatheter mitral valve repair with quality of life outcomes at 30 days and 1 year: analysis of the Transcatheter Valve Therapy Registry. JAMA Cardiol. 2018;3:1151-1159.
From the 1Cardiovascular Outcomes Research Institute, RWJ Barnabas Health-NBIMC, Newark, New Jersey; 2Rutgers New Jersey Medical School, Newark, New Jersey; and the 3Department of Surgery, Division of Cardiothoracic Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
The authors report that patient consent was provided for publication of the images used herein.
Manuscript submitted June 2, 2019, final version accepted June 12, 2019.
Address for correspondence: Alexis K. Okoh, MD, Cardiovascular Outcomes Research Institute, RWJ Barnabas Health-NBIMC, 201 Lyons Avenue, Suite G5, Newark, NJ 07112. Email: email@example.com