Transcatheter Mitral Valve Replacement Devices Research Articles

Multimodal preoperative imaging for transcatheter mitral valve replacement in the domestic sheep model

Preclinical in vivo evaluation is an essential step in the progression of new cardiac devices into patient use, with studies predominantly performed in the domestic sheep model. A growing area of interest in cardiac device development is transcatheter mitral valve replacement (TMVR). Clinically, multimodal imaging, or computed tomography (CT) and echocardiography (echo) are used extensively to preoperatively determine mitral valve morphology prior to an intervention, but there is no description on how these modalities can be implemented to support preclinical studies. The purpose of this study is to apply clinically relevant CT and echo acquisition and assessment techniques to a large group of naive research sheep in order to analyze and report modality-related effects on mitral valve dimensional reference intervals in the sheep model. To this end, fifty-five adult domestic sheep underwent preoperative CT and echo exams and resultant images were analyzed using a landmark-based multiplanar measurement protocol and compiled into a master dataset for statistical analysis. We found moderate agreement between CT and echo-derived measurements of the mitral valve in sheep and propose the first clinically-relevant dimensional indices for the sheep’s naive mitral valve which can be used to guide future studies evaluating novel TMVR devices. This study is the first of its kind in proposing a reproducible method for detailed examination of the mitral valve in the sheep model using clinically-relevant multimodal imaging. As in patients, CT and echo can reveal accurate native mitral valve dimensions in the sheep prior to preclinical TMVR studies.

Percutaneous balloon mitral valvuloplasty with shockwave lithotripsy for the treatment of calcific mitral valve stenosis.

Calcific mitral stenosis (calcific MS) presents a challenge for surgical treatment and is a contraindication for most contemporary transcatheter mitral valve replacement devices (TMVR), rendering patients with very limited therapeutic options. This study aims to assess the clinical and hemodynamic follow-up after mitral valve lithotripsy (MVL). All consecutive patients who underwent MVL to treat symptomatic calcific MS at St Michael's Hospital, Toronto, Canada, were included. Patients were deemed unsuitable for mitral surgery or TMVR after heart team assessment. Patients with rheumatic MS or ≥moderate mitral regurgitation (MR) were excluded. The primary endpoint was a reduction in the invasive mitral gradient by ≥50% without significant (≥moderate) MR. Fifteen patients underwent MVL between 2021 and 2023 with a mean age of 74 ± 9 years; 53% were female, with a mean STS score of 10% ± 0.1%. Following MVL, there was a reduction in the invasively measured mean trans-mitral gradient compared to baseline (14 mmHg vs. 6 mmHg; p < 0.05). The primary endpoint was achieved in 8 patients (53%) with no major procedural complications. At follow-up (median 90 days, IQR 58-115 days), 14 (93%) patients reported improved symptoms from New York Heart Association (NYHA) Class III-IV to NYHA Class I-II (p < 0.01) with stable echo-derived mean gradient (7.7 mmHg ± 2 mmHg vs. 8.4 mmHg ± 2.9 mmHg (p = 0.7). In selected patients with symptomatic inoperable calcific MS, MVL was safe and associated with significant short-term clinical and hemodynamic improvement. MVL may represent a new compassionate therapy for this challenging cohort. Further studies are needed to determine the long-term outcomes and help define the role of IVL technology in treating calcific valvular conditions.

Preemptive alcohol septal ablation prior to transcatheter mitral valve replacement.

Alcohol septal ablation (ASA) has been shown to increase the neo-left ventricular outflow tract (LVOT) area before transcatheter mitral valve replacement (TMVR) but there is little literature on its success and use with dedicated devices. To describe our experience with preemptive ASA to increase the predicted neo-LVOT area and its utility with both dedicated TMVR devices and balloon-expandable valves. All patients who underwent ASA for TMVR candidacy in our center between May 2018 and October 2022 and had computed tomography(CT) scans done before and after ASA were included. Each CT was assessed for the minimum predicted neo-LVOT area at end-systole, using a virtual valve of the desired TMVR device for each patient. The primary outcome was an increase in the predicted neo-LVOT area after ASA that was deemed sufficient for safe implantation of the desired TMVR device. The secondary outcome was the absence of acute LVOT obstruction after TMVR. A total of 12 patients underwent ASA and all but 1 (n = 11, 91.6%) achieved the primary outcome of having sufficient predicted neo-LVOT area to proceed with TMVR. The mean increase in neo-LVOT area after ASA was 126 ± 64 mm2 (median 119.5, interquartile range: 65.0-163.5 mm2 ). Two patients (16.7%) required a permanent pacemaker after ASA. Nine patients went on and underwent TMVR with their respective devices and none had LVOT obstruction after the procedure. Among the remaining three patients, one had insufficient neo-LVOT clearance after ASA, one had unrelated mortality before TMVR, and one had advanced heart failure before TMVR. In appropriately selected patients and at centers experienced with ASA, preemptive ASA can achieve sufficient neo-LVOT clearance for TMVR with a variety of devices in approximately 90% of patients.

Clinical outcomes of transcatheter mitral valve replacement: two-year results of the CHOICE-MI Registry.

Transcatheter mitral valve replacement (TMVR) using dedicated devices is an alternative therapy for high-risk patients with symptomatic mitral regurgitation (MR). This study aimed to assess the 2-year outcomes and predictors of mortality in patients undergoing TMVR from the multicentre CHOICE-MI Registry. The CHOICE-MI Registry included consecutive patients with symptomatic MR treated with 11different dedicated TMVR devices at 31 international centres. The investigated endpoints included mortality and heart failure hospitalisation rates, procedural complications, residual MR, and functional status. Multivariable Cox regression analysis was applied to identify independent predictors of 2-year mortality. Atotal of 400patients, median age 76 years (interquartile range [IQR] 71, 81), 59.5% male, EuroSCORE II 6.2% (IQR 3.8, 12.0), underwent TMVR. Technical success was achieved in 95.2% of patients. MR reduction to ≤1+ was observed in 95.2% at discharge with durable results at 1 and 2years. New York Heart Association Functional Class had improved significantly at 1 and 2years. All-cause mortality was 9.2% at 30days, 27.9% at 1year and 38.1% at 2years after TMVR. Chronic obstructive pulmonary disease, reduced glomerular filtration rate, and low serum albumin were independent predictors of 2-year mortality. Among the 30-day complications, left ventricular outflow tract obstruction, access site and bleeding complications showed the strongest impact on 2-year mortality. In this real-world registry of patients with symptomatic MR undergoing TMVR, treatment with TMVR was associated with adurable resolution of MR and significant functional improvement at 2years. Two-year mortality was 38.1%. Optimised patient selection and improved access site management are mandatory to improve outcomes.

Transcatheter Mitral Valve Replacement with Dedicated Devices.

Mitral regurgitation is the most common form of valvular heart disease. The anatomy and pathophysiology of mitral valve regurgitation are very complex, and dedicated devices are required for transcatheter mitral valve replacement in patients with a high or prohibitive surgical risk. In the United States, all transcatheter mitral valve replacement devices are still being studied and are not yet approved for commercial use. Early feasibility studies have demonstrated good technical success and short-term outcomes, but larger samples and longer-term outcomes still need to be assessed. Furthermore, significant advances in device technology, delivery systems, and implantation techniques are essential to avoid left ventricular outflow tract obstruction, and valvular and paravalvular regurgitation as well as ensuring good anchoring of the prosthesis.

Clinical Characteristics and Outcomes of Patients Screened for but Deemed Clinically Not Suitable for Transcatheter Mitral Valve Replacement: DECLINE-TMVR Registry.

Transcatheter therapies are a recognized alternative intervention in patients with severe mitral regurgitation who are at high surgical risk. The purpose of this study was to characterize patients screened for transcatheter mitral valve replacement (TMVR), establish the clinical and anatomic reasons for unsuitability, and determine clinical course and early outcomes. International multicentre registry was conducted of consecutive patients screened for TMVR at 12 centres in Europe, the United States, and Canada between April 2015 and September 2018. Patient-level retrospective data were collected for all patients screened. From a total of 294 patients, 87 (30%) patients were suitable for and underwent TMVR, whereas 207 (70%) patients were unsuitable for TMVR. There was no difference in Society of Thoracic Surgeons predicted risk of mortality (6.3% ± 4.3% vs 6.7 ± 6.1%, P= 0.52) for mitral valve replacement between the groups. The most common reasons for TMVR unsuitability were mitral annular size outside therapeutic range (28%) and small, predicted neo-LVOT (25%). Preprocedural multidetector computed tomographic demonstrated that patients unsuitable for TMVR had smaller predicted neo-left ventricular outflow tract (LVOT) area (318 ±192 mm2 vs 495 ± 202 mm2, P= 0.04). At 30 days, there was no difference in rates of rehospitalization (8% vs 8%, P= 0.21), stroke (1% vs 2%, P= 0.42), or mortality (4% vs 10%, P= 0.10), unadjusted for procedural risk, between unsuitable for TMVR and TMVR groups, respectively. Two-thirds of patients failed screening as anatomically unsuitable for TMVR. The findings of this study have important clinical implications, highlighting an unmet clinical need and provide a target for design innovation in future iterations of TMVR devices.

Transcatheter Mitral Valve Replacement in Patients with Mitral Annular Calcification: A Review.

Mitral annular calcification (MAC) is a progressive degenerative calcification of the mitral valve (MV) that is associated with mitral stenosis, regurgitation or both. Patients with MAC are poor candidates for MV surgery because of technical challenges and high peri-operative mortality. Transcatheter MV replacement (TMVR) has emerged as an option for such high surgical risk patients. This has been described with the use of the SAPIEN transcatheter heart valve (valve-in-MAC) and dedicated TMVR devices. Careful anatomic assessment is important to avoid complications of TMVR, such as left ventricular outflow tract obstruction, valve migration, embolization and paravalvular mitral regurgitation. In this review, we discuss the pathology, importance of preprocedural multimodality imaging for optimal patient selection, clinical outcomes and complications associated with TMVR in patients with MAC.

Transcatheter Mitral Valve Repair or Replacement: Competitive or Complementary?

Over the last two decades, transcatheter devices have been developed to repair or replace diseased mitral valves (MV). Transcatheter mitral valve repair (TMVr) devices have been proven to be efficient and safe, but many anatomical structures are not compatible with these technologies. The most significant advantage of transcatheter mitral valve replacement (TMVR) over transcatheter repair is the greater and more reliable reduction in mitral regurgitation. However, there are also potential disadvantages. This review introduces the newest TMVr and TMVR devices and presents clinical trial data to identify current challenges and directions for future research.

Randomized Trials Are Needed for Transcatheter Mitral Valve Replacement.

Transcatheter mitral valve replacement (TMVR) is a new therapy for treating symptomatic mitral regurgitation (MR) and stenosis. The proposed benefit of TMVR is the predictable, complete elimination of MR, which is less certain with transcatheter repair technologies such as TEER (transcatheter edge-to-edge repair). The potential benefit of MR elimination with TMVR needs to be rigorously evaluated against its risks which include relative procedural invasiveness, need for anticoagulation, and chronic structural valve deterioration. Randomized controlled trials (RCTs) are a powerful method for evaluating the safety and effectiveness of TMVR against current standard of care transcatheter therapies, such as TEER. RCTs not only help with the assessment of benefits and risks, but also with policies for determining operator or institutional requirements, resource utilization, and reimbursement. In this paper, the authors provide recommendations and considerations for designing pivotal RCTs for first-in-class TMVR devices.

Transcatheter Mitral Valve Replacement: Current Evidence and Concepts.

Over the past decade, several transcatheter devices have been developed to address the treatment of severe mitral regurgitation (MR) in patients at high surgical risk, mainly aimed at repairing the native mitral valve (MV). MV repair devices have recently been shown to have high efficacy and safety. However, to replicate promising trial results, specific anatomical and pathophysiological criteria have to be met and operators need a high level of experience. As yet, the longer-term durability of transcatheter MV repair remains unknown. Transcatheter MV replacement (TMVR) might be a treatment option able to target various anatomies, reliably abolish MR, and foster ease of use with a standardised implantation protocol. This review presents upcoming TMVR devices and available data and discusses how TMVR might further advance the field of transcatheter treatment of MR.

Early results of a real-world series with two transapical transcatheter mitral valve replacement devices

AimsTranscatheter mitral valve replacement (TMVR) with dedicated devices promises to fill the treatment gap between open-heart surgery and edge-to-edge repair for patients with severe mitral regurgitation (MR). We herein present a single-centre experience of a TMVR series with two transapical devices.Methods and resultsA total of 11 patients were treated with the Tendyne™ (N = 7) or the Tiara™ TMVR systems (N = 4) from 2016 to 2020 either as compassionate-use procedures or as commercial implants. Clinical and echocardiographic data were collected at baseline, discharge and follow-up and are presented in accordance with the Mitral Valve Academic Research Consortium (MVARC) definitions.The study cohort [age 77 years (73, 84); 27.3% male] presented with primary (N = 4), secondary (N = 5) or mixed (N = 2) MR etiology. Patients were symptomatic (all NYHA III/IV) and at high surgical risk [logEuroSCORE II 8.1% (4.0, 17.4)]. Rates of impaired RV function (72.7%), severe pulmonary hypertension (27.3%), moderate or severe tricuspid regurgitation (63.6%) and prior aortic valve replacement (63.6%) were high. Severe mitral annulus calcification was present in two patients. Technical success was achieved in all patients. In 90.9% (N = 10) MR was completely eliminated (i.e. no or trace MR). Procedural and 30-day mortality were 0.0%. At follow-up NYHA class was I/II in the majority of patients. Overall mortality after 3 and 6 months was 10.0% and 22.2%.ConclusionsTMVR was performed successfully in these selected patients with complete elimination of MR in the majority of patients. Short-term mortality was low and most patients experienced persisting functional improvement.Graphic abstract

Transcatheter Mitral Valve Replacement: Procedural Planning, Utility, and Applicability.

Since the first native transcatheter mitral valve implantation in 2012, transcatheter mitral valve replacement (TMVR) has expanded its use to degenerated bioprostheses, failed annuloplasty ring repair, and mitral annular calcification. However, high-screen failure rates in trials have persisted due to predicted left ventricular outflow tract obstruction and unfavorable anatomy. Preprocedural planning in this patient population with multidetector computed tomography and transesophageal echocardiography is paramount to intraprocedural success. In patients with favorable left ventricular outflow tract anatomy who are not surgical candidates, the transseptal approach is preferred. In those who are surgical candidates, TMVR can be performed via a transapical or transatrial approach. Currently, a plethora of TMVR devices targeting the native mitral pathologies are undergoing clinical trials. Data have consistently shown the greatest benefit of this procedure in native mitral regurgitation and failed bioprostheses rather than failed annuloplasty rings or mitral annular calcification. With technological advancement and careful patient selection, this therapy will serve as a complement to surgical and TMV repair and will continue to expand to address MV diseases in a broader patient population.

Screening for transcatheter mitral valve replacement: a decision tree algorithm.

The high frequency of screening failure for anatomical reasons in patients with severe mitral valve regurgitation (MR) is a limiting factor in the screening process for transcatheter mitral valve replacement (TMVR). However, data on optimal patient selection are scarce. The present study aimed to develop a screening algorithm based on TMVR screening data. A total of 195 screenings for six different TMVR devices were performed in 94 high-risk patients with severe MR. We compared baseline echocardiographic and multislice computed tomography (MSCT) parameters between the subgroups of patients accepted (N=33) and rejected for TMVR (N=61). Reasons for screening failure were assessed, and a decision tree algorithm was statistically derived. Reasons for screening failure were small LV dimensions (30.6%), small (7.5%) or large (22.5%) annular size, potential risk of LVOT obstruction (22.0%) or mitral annulus calcification (15.6%). A four-step decision tree algorithm to assess TMVR eligibility was developed resulting in an AUC of 0.80 (95% CI: 0.71, 0.89, p<0.0001). This study presents the first screening algorithm to assess anatomical eligibility for TMVR in patients with severe MR, based on simple MSCT criteria. Given the high rate of TMVR screening failure, this algorithm may facilitate the identification of potential TMVR candidates.

Transcatheter Mitral Valve Replacement: State of the Art.

The emergence of transcatheter aortic valve replacement (TAVR) has segued the development of transcatheter mitral valve (MV) repair devices. Transcatheter mitral valve repair has become a well-established alternative for patients with severe primary and secondary mitral regurgitation (MR) and with a perceived surgical risk. Transcatheter mitral valve replacement (TMVR) could become a more complete form of reduction of severe MR compared to MV repair devices, albeit with significant engineering challenges and all the risks associated with a bioprosthetic heart valve. The development of TMVR devices has become prominent while companies race to become the first commercially available system. Careful consideration of design challenges should be conducted by the developmental companies to ensure successful devices. Preclinical and clinical trials have shown promising results, showcasing the feasibility of total valve replacement utilizing transcatheter procedure techniques. Further development, testing, and trials need to be conducted before TMVR can become a sensible MR treatment. This review describes design challenges and considerations along with the state of the art, involving designs in both clinical and preclinical stages.

What role for transcatheter mitral valve replacement?

Despite the safety and efficacy of transmitral valve repair techniques, transcatheter mitral valve replacement (TMVR) has emerged as a potential treatment option for patients with severe mitral regurgitation at high or prohibitive surgical risk. To date, over 250 high-risk patients with severe mitral regurgitation have been treated with 10 different TMVR devices, demonstrating the feasibility of this technique. Parallel to the potential advantages of this procedure (reproducible mitral regurgitation reduction, possibility of targeting all potential anatomic variations), many challenges has emerged during the design and implantation phases. Further larger studies with longer follow-up are needed to evaluate safety and efficacy of TMVR.

Functional Mitral Regurgitation: An Interventional Cardiologist's Perspective.

Functional mitral regurgitation (FMR) is common in patients with heart failure and portends a poor prognosis. The etiology is secondary to nonischemic or ischemic (postmyocardial infarction) adverse remodeling. Treatment includes guideline-directed medical therapy, cardiac resynchronization therapy, and in some cases, surgical repair or replacement. Transcatheter mitral valve (MV) repair with the MitraClip device is approved in patients with degenerative MR and is currently under investigation for use in FMR, as are several transcatheter MV replacement devices. This review discusses the basis of FMR pathophysiology, classification, and prognosis; provides an overview of current therapeutic approaches; examines the available literature on the use of MitraClip in patients with FMR; and provides insight into ongoing clinical trials and new investigational devices for the treatment of FMR.

Transcatheter mitral valve replacement

Mitral valve disease is a growing clinical problem. Surgical mitral valve repair and replacement remains the treatment of choice with excellent long-term clinical outcomes. However, a large number of symptomatic patients were deemed too high-risk undergoing surgical correction. Catheter-based technology has been in development to address this unmet need. Transcatheter mitral valve replacement devices are such technology and are currently undergoing clinical investigation. A systematic overview is being presented in the article.

Transcatheter Mitral Valve Replacement for Native and Failed Bioprosthetic Mitral Valves.

Transcatheter mitral valve replacement (TMVR) is a novel approach for treatment of severe mitral regurgitation. A number of TMVR devices are currently undergoing feasibility trials using both transseptal and transapical routes for device delivery. Overall experience worldwide is limited to fewer than 200 cases. At present, the 30-day mortality exceeds 30% and is attributable to both patient- and device-related factors. TMVR has been successfully used to treat patients with degenerative mitral stenosis (DMS) as well as failed mitral bioprosthesis and mitral repair using transcatheter mitral valve-in-valve (TMViV)/valve-in-ring (ViR) repair. These patients are currently treated with devices designed for transcatheter aortic valve replacement. Multicenter registries have been initiated to collect outcomes data on patients currently undergoing TMViV/ViR and TMVR for DMS and have confirmed the feasibility of TMVR in these patients. However, the high periprocedural and 30-day event rates underscore the need for further improvements in device design and multicenter randomized studies to delineate the role of these technologies in patients with mitral valve disease.

Quantitative multi-slice computed tomography assessment of the mitral valvular complex for transcatheter mitral valve interventions part 2: geometrical measurements in patients with functional mitral regurgitation.

Transcatheter mitral valve replacement (TMVR) is an emerging technology with the potential to treat patients with mitral regurgitation at excessive risk for mitral valve surgery. Geometrical measurements of the mitral valvular complex may have implications for the design of TMVR devices and for patient selection. This study sought to quantify the dynamic geometry of the mitral valvular complex in patients with significant functional mitral regurgitation (FMR) using multi-slice computed tomography (MSCT). MSCT images were acquired in 32 patients with symptomatic, significant FMR. Two independent observers analysed image sets using a dedicated software package and a standard measurement methodology. In patients with FMR, the mean mitral annulus intercommissural and aorto-mural diameters were, respectively, 41.5±5.2 mm and 38.7±5.9 mm in systole, and were 41.5±4.4 mm and 40.0±4.7 mm in diastole. In patients without MR, the diameters were, respectively, 33.6±5.1 mm and 28.8±8.0 mm in systole, and 36.2±4.5 mm and 31.6±7.9 mm in diastole. The obstacle-free zone below the mitral annulus averaged more than 20.0 mm and varied by less than 1 mm between systole and diastole, which is not statistically significant. The aorto-mitral angle was 129.7±10.5° in systole and 131.0±9.4° in diastole. The mitral annulus is larger in dimension, more circular, and less dynamic in patients with FMR. The obstacle-free zone below the mitral annulus is relatively constant during the cardiac cycle. Measurements of the mitral valvular apparatus vary considerably between patients, which suggests that tridimensional imaging will play an important role in the sizing of TMVR devices.

Quantitative multi-slice computed tomography assessment of the mitral valvular complex for transcatheter mitral valve interventions part 1: systematic measurement methodology and inter-observer variability.

Transcatheter mitral valve replacement (TMVR) is an emerging technology with the potential to treat patients with severe mitral regurgitation at excessive risk for surgical mitral valve surgery. Multimodality imaging of the mitral valvular complex and surrounding structures will be an important component for patient selection for TMVR. Our aim was to describe and evaluate a systematic multi-slice computed tomography (MSCT) image analysis methodology that provides measurements relevant for transcatheter mitral valve replacement. A systematic step-by-step measurement methodology is described for structures of the mitral valvular complex including: the mitral valve annulus, left ventricle, left atrium, papillary muscles and left ventricular outflow tract. To evaluate reproducibility, two observers applied this methodology to a retrospective series of 49 cardiac MSCT scans in patients with heart failure and significant mitral regurgitation. For each of 25 geometrical metrics, we evaluated inter-observer difference and intra-class correlation. The inter-observer difference was below 10% and the intra-class correlation was above 0.81 for measurements of critical importance in the sizing of TMVR devices: the mitral valve annulus diameters, area, perimeter, the inter-trigone distance, and the aorto-mitral angle. MSCT can provide measurements that are important for patient selection and sizing of TMVR devices. These measurements have excellent inter-observer reproducibility in patients with functional mitral regurgitation.