Valve Hemodynamics by Valve Size and 1-Year Survival Following Implantation of the Portico Valve in the Multicenter CONFIDENCE Registry.

Background: The CONtrolled delivery For ImproveD outcomEs with cliNiCal Evidence registry was initiated to characterize the clinical safety and device performance from experienced transcatheter aortic valve implantation (TAVI) centers in Europe and Australia that use the Portico valve to treat patients with severe aortic stenosis. We herein report for the first time the valve performance at 30-day across all implanted valve sizes and the 1-year survival from this registry. Methods: This was a prospective, multicenter, single-arm observational clinical investigation of patients clinically indicated for implantation of a Portico valve in experienced TAVI centers. Patients were treated with a commercially available valve (size 23, 25, 27, or 29 mm) using either the first-generation delivery system (DS) (n = 501) or the second-generation (FlexNav) DS (n = 500). Adverse events were adjudicated by an independent clinical events committee according to Valve Academic Research Consortium-2 criteria. Echocardiographic outcomes were assessed at 30 days by an independent core laboratory, and a survival check was performed at 1 year. Results: We enrolled 1001 patients (82.0 years, 62.5% female, 63.7% New York Heart Association functional class III/IV at baseline) from 27 clinical sites in 8 countries across Europe and one site in Australia. Implantation of a single valve was successful in 97.5% of subjects. Valve hemodynamics at 30 days were substantially improved relative to baseline, with large aortic valve areas and low mean gradients across all implanted valve sizes (aortic valve areas were 1.7 ± 0.4, 1.7 ± 0.5, 1.8 ± 0.5, and 2.0 ± 0.5 cm2, and mean gradients were 7.0 ± 2.7, 7.5 ± 4.7, 7.3 ± 3.3, and 6.4 ± 3.3 mmHg for 23, 25, 27, and 29 mm valve sizes, respectively). Across all implanted valve sizes, most patients (77.1%) had no patient-prosthesis mismatch. Death from any cause within 1 year occurred in 13.7% of the patients in the first-generation DS group as compared with 11.0% in the second-generation DS group (p = 0.2). Conclusions: The Portico valve demonstrated excellent hemodynamic performance across all valve sizes in a large cohort of subjects implanted in experienced TAVI centers. One-year survival rates were favorable when using both the first-generation and second-generation (FlexNav) DSs in this high-risk cohort. ClinicalTrialsgov Identifier: NCT03752866.

Effect of Ascending Aortic Curvature on Flow in the Sinus and Neo-sinus Following TAVR: A Patient-Specific Study.

Patient-specific aortic geometry and its influence on the flow in the vicinity of Transcatheter Aortic Valve (TAV) has been highlighted in numerous studies using both in silico and in vitro experiments. However, there has not yet been a detailed Particle Image Velocimetry (PIV) experiment conducted to quantify the relationship between the geometry, flow downstream of TAV, and the flow in the sinus and the neo-sinus. We tested six different patient-specific aorta models with a 26-mm SAPIEN 3 valve (Edwards Lifesciences, Irvine, CA, USA) in a left heart simulator with coronary flow. Velocities in all three cusps and circulation downstream of TAV were computed to evaluate the influence of the ascending aorta curvature on the flow field. The in vitro analysis showed that the patient-specific aortic curvature had positive correlation to the circulation in the ascending aorta (p = 0.036) and circulation had negative correlation to the particle washout time in the cusps (p = 0.011). These results showed that distinct vortical flow patterns in the ascending aorta as the main jet impinges on the aortic wall causes a recirculation region that facilitates the flow back into the sinus and the neo-sinus, thus reducing the risk of flow stagnation and washout time.

Effect of leaflet laceration on transcatheter aortic valve replacement fluid mechanics and comparison with surgical aortic valve replacement.

BACKGROUND: Leaflet thrombosis after surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) may be caused by blood flow stagnation in the native and neosinus regions. To date, aortic leaflet laceration has been used to mitigate coronary obstruction following TAVR; however, its influence on the fluid mechanics of the native and neosinus regions is poorly understood. This in vitro study compared the flow velocities and flow patterns in the setting of SAVR vs TAVR with and without aortic leaflet lacerations. METHODS: Two valves, (23-mm Perimount and 26-mm SAPIEN 3; Edwards Lifesciences) were studied in a validated mock flow loop under physiologic conditions. Neosinus and native sinus fluid mechanics were quantified using particle image velocimetry in the left and noncoronary cusp, with an increasing number of aortic leaflets lacerated or removed. RESULTS: Across all conditions, SAVR had the highest average sinus and neosinus velocities, and this value was used as a reference to compare against the TAVR conditions. With an increasing number of leaflets lacerated or removed with TAVR, the average sinus and neosinus velocities increased from 25% to 70% of SAVR flow (100%). Diastolic velocities were substantially augmented by leaflet laceration. Also, the shorter frame of the SAVR led to higher flow velocities compared with the longer frame of the TAVR, even after complete leaflet removal. CONCLUSIONS: Leaflet laceration augmented TAVR native and neosinus flow fields, approaching that of SAVR. These findings may have potential clinical implications for the use of single or multiple leaflet lacerations to reduce leaflet thrombosis and thus potentially improve TAVR durability.

Effect of Native Aortic Leaflet Geometry Modification on Transcatheter Aortic Valve Neo-sinus and Aortic Sinus Flow: An In-vitro Study.

PURPOSE: Leaflet thrombosis is a potentially fatal complication after transcatheter aortic valve replacement (TAVR). Blood flow stagnation in the neo-sinus and aortic sinuses are associated with increased thrombus severity. Native aortic leaflet modification may be a potential strategy to improve the neo-sinus and aortic sinus fluid dynamics. However, limited data exist on the effect of leaflet geometry modification on the flow within the neo-sinus and aortic sinus regions. We evaluate the effect of aortic leaflet modification on the neo-sinus and aortic sinus flow stagnation after simulated TAVR. METHODS: Particle image velocimetry measurements were performed under nominal (5 LPM) and low (2.5 LPM) cardiac output conditions for an intact leaflet (control) case, and 3 modified leaflet geometries. Aortic leaflet geometry modification via leaflet splay was simulated with increasing splay geometry (leaflet splay distance: 5 mm-narrow, 10 mm-medium, and 20 mm-wide). RESULTS: Leaflet geometry modification influenced flow features throughout the cardiac cycle, at both cardiac outputs, and allowed for flow communication between the neo-sinus and aortic sinus regions compared to the control. In the aortic sinus, flow stagnation reduced by over 64% at 5LPM, and over 36% at 2.5LPM for all simulated modified leaflet geometries compared to the control. However, only the medium and wide splay geometries enabled a reduction in neo-sinus flow stagnation compared to the control case. CONCLUSIONS: These findings suggest that aortic leaflet geometry modification (of at least 10 mm leaflet splay distance) may reduce flow stasis and potentially decrease valve thrombosis risk.

Early outcomes following transatrial transcatheter mitral valve replacement in patients with severe mitral annular calcification.

OBJECTIVE: Implantation of a transcatheter valve-in-mitral annular calcification (ViMAC) has emerged as an alternative to traditional surgical mitral valve (MV) replacement. Previous studies evaluating ViMAC aggregated transseptal, transapical, and transatrial forms of the procedure, leaving uncertainty about each technique's advantages and disadvantages. Thus, we sought to evaluate clinical outcomes specifically for transatrial ViMAC from the largest multicenter registry to-date. METHODS: Patients with symptomatic MV dysfunction and severe MAC who underwent ViMAC were enrolled from 12 centers across the United States and Europe. Clinical characteristics, procedural details, and clinical outcomes were abstracted from the electronic record. The primary end point was all-cause mortality. RESULTS: We analyzed 126 patients who underwent ViMAC (median age 76 years [interquartile range {IQR}, 70-82 years], 28.6% female, median Society of Thoracic Surgeons score 6.8% [IQR, 4.0-11.4], and median follow-up 89 days [IQR, 16-383.5]). Sixty-one (48.4%) had isolated mitral stenosis, 25 (19.8%) had isolated mitral regurgitation (MR), and 40 (31.7%) had mixed MV disease. Technical success was achieved in 119 (94.4%) patients. Thirty (23.8%) patients underwent concurrent septal myectomy, and 8 (6.3%) patients experienced left ventricular outflow tract obstruction (7/8 did not undergo myectomy). Five (4.2%) patients of 118 with postprocedure echocardiograms had greater than mild paravalvular leak. Thirty-day and 1-year all-cause mortality occurred in 16 and 33 patients, respectively. In multivariable models, moderate or greater MR at baseline was associated with increased risk of 1-year mortality (hazard ratio, 2.31; 95% confidence interval, 1.07-4.99, P = .03). CONCLUSIONS: Transatrial ViMAC is safe and feasible in this selected, male-predominant cohort. Patients with significant MR may derive less benefit from ViMAC than patients with mitral stenosis only.

Assessing the Hemodynamic Impact of Anterior Leaflet Laceration in Transcatheter Mitral Valve Replacement: An in silico Study.

Background: A clinical study comparing the hemodynamic outcomes of transcatheter mitral valve replacement (TMVR) with vs. without Laceration of the Anterior Mitral leaflet to Prevent Outflow Obstruction (LAMPOON) has never been designed nor conducted. Aims: To quantify the hemodynamic impact of LAMPOON in TMVR using patient-specific computational (in silico) models. Materials: Eight subjects from the LAMPOON investigational device exemption trial were included who had acceptable computed tomography (CT) data for analysis. All subjects were anticipated to be at prohibitive risk of left ventricular outflow tract (LVOT) obstruction from TMVR, and underwent successful LAMPOON immediately followed by TMVR. Using post-procedure CT scans, two 3D anatomical models were created for each subject: (1) TMVR with LAMPOON (performed procedure), and (2) TMVR without LAMPOON (virtual control). A validated computational fluid dynamics (CFD) paradigm was then used to simulate the hemodynamic outcomes for each condition. Results: LAMPOON exposed on average 2 ± 0.6 transcatheter valve cells (70 ± 20 mm2 total increase in outflow area) which provided an additional pathway for flow into the LVOT. As compared to TMVR without LAMPOON, TMVR with LAMPOON resulted in lower peak LVOT velocity, lower peak LVOT gradient, and higher peak LVOT effective orifice area by 0.4 ± 0.3 m/s (14 ± 7% improvement, p = 0.006), 7.6 ± 10.9 mmHg (31 ± 17% improvement, p = 0.01), and 0.2 ± 0.1 cm2 (17 ± 9% improvement, p = 0.002), respectively. Conclusion: This was the first study to permit a quantitative, patient-specific comparison of LVOT hemodynamics following TMVR with and without LAMPOON. The LAMPOON procedure achieved a critical increment in outflow area which was effective for improving LVOT hemodynamics, particularly for subjects with a small neo-left ventricular outflow tract (neo-LVOT).

Dynamic nature of the LVOT following transcatheter mitral valve replacement with LAMPOON: new insights from post-procedure imaging.

AIMS: To characterize the dynamic nature of the left ventricular outflow tract (LVOT) geometry and flow rate in patients following transcatheter mitral valve replacement (TMVR) with anterior leaflet laceration (LAMPOON) and derive insights to help guide future patient selection. METHODS AND RESULTS: Time-resolved LVOT geometry and haemodynamics were analysed with post-procedure computed tomography and echocardiography in subjects (N = 19) from the LAMPOON investigational device exemption trial. A novel post hoc definition for LVOT obstruction was employed to account for systolic flow rate and quality of life improvement [obstruction was defined as LVOT gradient >30 mmHg or LVOT effective orifice area (EOA) ≤1.15 cm2]. The neo-LVOT and skirt neo-LVOT were observed to vary substantially in area throughout systole (64 ± 27% and 25 ± 14% change in area, respectively). The peak systolic flow rate occurred most commonly just prior to mid-systole, while minimum neo-LVOT (and skirt neo-LVOT) area occurred most commonly in early-diastole. Subjects with LVOT obstruction (n = 5) had smaller skirt neo-LVOT values across systole. Optimal thresholds for skirt neo-LVOT area were phase-specific (260, 210, 200, and 180 mm2 for early-systole, peak flow, mid-systole, and end-systole, respectively). CONCLUSION: The LVOT geometry and flow rate exhibit dynamic characteristics following TMVR with LAMPOON. Subjects with LVOT obstruction had smaller skirt neo-LVOT areas across systole. The authors recommend the use of phase-specific threshold values for skirt neo-LVOT area to guide future patient selection for this procedure. LVOT EOA is a 'flow-independent' metric which has the potential to aid in characterizing LVOT obstruction severity.

Impact of Anchor Location on Mitral Neochordae Forces: An In Vitro Study.

PURPOSE: This study examined changes in force distribution between the neochordae corresponding to different ventricular anchor locations. DESCRIPTION: Seven porcine mitral valves were mounted in a left heart simulator. Neochordae (expanded polytetrafluoroethylene) originated from either a simulated left ventricular apex, papillary muscle base, or papillary muscle tip location. The neochordae were attached at three sites along the P2 leaflet segment: P2Lateral; P2Center, and P2Medial. Mitral regurgitation was induced by cutting posterior leaflet P2 marginal chordae. The forces on each neochord required to restore normal mitral valve coaptation were quantified for different ventricular anchoring origins and leaflet insertion sites. EVALUATION: The results showed that under both normotensive and hypertensive conditions, the force exerted was much higher at P2Center than either P2Lateral or P2Medial, independent of ventricular anchor location. Also, forces on both P2Lateral and P2Medial were not statistically different. CONCLUSIONS: Artificial neochordae treatment for all anchoring locations was effective in correcting induced mitral regurgitation. The P2 central neochordae had a significantly higher force than both lateral neochords under all conditions.

Balloon-Augmented Leaflet Modification With Bioprosthetic or Native Aortic Scallop Intentional Laceration to Prevent Iatrogenic Coronary Artery Obstruction and Laceration of the Anterior Mitral Leaflet to Prevent Outflow Obstruction: Benchtop Validation and First In-Man Experience.

BACKGROUND: Bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction (BASILICA) and laceration of the anterior mitral leaflet to prevent outflow obstruction (LAMPOON) reduce the risk of coronary and left ventricular outflow obstruction obstruction during transcatheter aortic valve replacement and transcatheter mitral valve replacement. Despite successful laceration, BASILICA or LAMPOON may fail to prevent obstruction caused by inadequate leaflet splay in patients having challenging anatomy such as very small valve-to-coronary distance, diffusely calcified, rigid leaflets, or undergoing transcatheter aortic valve replacement inside existing transcatheter aortic valve replacement. We describe a novel technique of balloon-augmented (BA) leaflet laceration to enhance leaflet splay. METHODS: We measured the incremental leaflet splay from BA-BASILICA in vitro. From November 2019 to March 2021, 16 patients underwent BA-BASILICA and 4 BA-LAMPOON at 3 centers. RESULTS: BA-BASILICA increased benchtop leaflet tip splay 17%, maximum splay angle 30%, and splay area 23%, resulting in a more rounded apex and larger effective area. Sixteen patients at risk for inadequate BASILICA leaflet splay, including 4 transcatheter aortic valve replacement inside existing transcatheter aortic valve replacement, underwent BA-BASILICA. All had successful leaflet laceration. One had coronary obstruction requiring immediate orthotopic stenting. Two underwent elective orthotopic coronary stenting through the transcatheter valve cells for leaflet prolapse without coronary ischemia. There were no deaths during the procedure or at 30 days. Four patients at risk for inadequate anterior mitral leaflet splay underwent BA-LAMPOON. All had successful target leaflet laceration without left ventricular outflow obstruction obstruction or procedural death. One died within 30 days. CONCLUSIONS: BA leaflet laceration enhances leaflet splay in vitro and may allow transcatheter aortic valve replacement and transcatheter mitral valve replacement in patients otherwise ineligible for traditional BASILICA or LAMPOON due to challenging anatomy. Graphic Abstract: A graphic abstract is available for this article.

The Art of SAPIEN 3 Transcatheter Mitral Valve Replacement in Valve-in-Ring and Valve-in-Mitral-Annular-Calcification Procedures.

The SAPIEN 3 is the only transcatheter heart valve commercially available for compassionate transcatheter mitral valve replacement in patients with previous mitral surgical rings and mitral annular calcification (valve in ring [VIR] and valve in mitral annular calcification [VIM]). Reported outcomes have been inconsistent or poor. The review provides an overview of the authors' approach to achieve largely consistent results despite the intrinsic limitations of SAPIEN 3 VIM and VIR. The approach includes bedside modifications of the valve implant, the delivery system, and of the cardiac substrate itself. Until purpose-built devices are readily available, VIR and VIM procedures will require aggressive multidisciplinary cooperation, meticulous planning and execution, and postprocedure management by experienced, high-volume operators.

A Simplified In Silico Model of Left Ventricular Outflow in Patients After Transcatheter Mitral Valve Replacement with Anterior Leaflet Laceration.

In silico modeling has been proposed as a tool to simulate left ventricular (LV) outflow tract (LVOT) obstruction in patients undergoing transcatheter mitral valve replacement (TMVR). This study validated a simplified approach to simulate LV outflow hemodynamics in the setting of TMVR with anterior leaflet laceration, a clinical technique used to mitigate the risk of LVOT obstruction. Personalized, 3-dimensional computational fluid dynamics models were developed from computed tomography images of six patients who underwent TMVR with anterior leaflet laceration. LV outflow hemodynamics were simulated using the patient-specific anatomy and the peak systolic flow rate as boundary conditions. The peak outflow velocity, a clinically relevant hemodynamic metric, was extracted from each simulation (vsim-peak) and compared with the clinical measurement from Doppler echocardiography (vclin-peak) for validation. In silico models were successfully developed and implemented for all patients. The pre-processing time was 2 h per model and the simulation could be completed within 3 h. In three patients, the lacerated anterior leaflet exposed open cells of the transcatheter valve to flow. Good agreement was obtained between vsim-peak and vclin-peak (r = 0.97, p < 0.01) with average discrepancies of 5 ± 2% and 14 ± 1% for patients with exposed and unexposed cells of the transcatheter valve, respectively. The proposed in silico modeling paradigm therefore simulated LV outflow hemodynamics in a time-efficient manner and demonstrated good agreement with clinical measurements. Future studies should investigate the ability of this paradigm to support clinical applications.

Effect of Edge-to-Edge Mitral Valve Repair on Chordal Strain: Fluid-Structure Interaction Simulations.

Edge-to-edge repair for mitral valve regurgitation is being increasingly performed in high-surgical risk patients using minimally invasive mitral clipping devices. Known procedural complications include chordal rupture and mitral leaflet perforation. Hence, it is important to quantitatively evaluate the effect of edge-to-edge repair on chordal integrity. in this study, we employ a computational mitral valve model to simulate functional mitral regurgitation (FMR) by creating papillary muscle displacement. Edge-to-edge repair is then modeled by simulated coaptation of the mid portion of the mitral leaflets. in the setting of simulated FMR, edge-to-edge repair was shown to sustain low regurgitant orifice area, until a two fold increase in the inter-papillary muscle distance as compared to the normal mitral valve. Strain in the chordae was evaluated near the papillary muscles and the leaflets. Following edge-to-edge repair, strain near the papillary muscles did not significantly change relative to the unrepaired valve, while strain near the leaflets increased significantly relative to the unrepaired valve. These data demonstrate the potential for computational simulations to aid in the pre-procedural evaluation of possible complications such as chordal rupture and leaflet perforation following percutaneous edge-to-edge repair.

Novel In Vitro Test Systems and Insights for Transcatheter Mitral Valve Design, Part I: Paravalvular Leakage.

While transcatheter mitral valve (TMV) replacement technology has great clinical potential for surgically inoperable patients suffering from mitral regurgitation, no TMV has yet achieved regulatory approval. The diversity of devices currently under development reflects a lack of consensus regarding optimal design approaches. In Part I of this two-part study, a test system was developed for the quantification of paravalvular leakage (PVL) following deployment of a TMV or TMV-like device in pressurized, explanted porcine hearts (N = 7). Using this system, PVL rate was investigated as a function of steady trans-mitral pressure (ΔP), TMV shape, and TMV-annular oversizing, using a series of "mock TMV plug" devices. Across all devices, PVL was found to approximately trend with the square of ΔP. PVL rates were approximately 0-15 mL/s under hypotensive pressure, 10-40 mL/s under normotension, and 30-85 mL/s under severe hypertension. D-shaped devices significantly reduced PVL vs. circular devices; however, this effect was diminished upon oversizing to the annulus by 6 mm inter-trigonal distance. In conclusion, this steady pressure, in vitro test system was effective to compare PVL performance across TMV-like designs. PVL exhibited complex dynamics in terms of its response to transvalvular pressure and TMV profile.

Novel In Vitro Test Systems and Insights for Transcatheter Mitral Valve Design, Part II: Radial Expansion Forces.

Transcatheter mitral valve (TMV) replacement technology has great clinical potential for surgically inoperable patients suffering from mitral regurgitation. An important goal for robust TMV design is maximizing the likelihood of achieving a geometry post-implant that facilitates optimal performance. To support this goal, improved understanding of the annular forces that oppose TMV radial expansion is necessary. In Part II of this study, novel circular and D-shaped Radial Expansion Force Transducers (C-REFT and D-REFT) were developed and employed in porcine hearts (N = 12), to detect the forces required to radially expand the mitral annulus to discrete oversizing levels. Forces on both the septal-lateral and inter-commissural axes (FSL and FIC) scaled with device size. The D-REFT experienced lower FSL than the C-REFT (19.8 ± 7.4 vs. 17.4 ± 10.8 N, p = 0.002) and greater FIC (31.5 ± 14.0 vs. 36.9 ± 16.2 N; p = 0.002), and was more sensitive to degree of oversizing. Across all tests, FIC/FSL was 2.21 ± 1.33, likely reflecting low resistance to radial expansion at the aorto-mitral curtain. In conclusion, the annular forces opposing TMV radial expansion are non-uniform, and depend on final TMV shape and size. Based on this two-part study, we propose that radial force applied at the commissural aspect of the annulus has the most potent effect on paravalvular sealing.

Transcatheter Mitral Valve Planning and the Neo-LVOT: Utilization of Virtual Simulation Models and 3D Printing.

PURPOSE OF REVIEW: Transcatheter mitral valve replacement (TMVR) is an emerging alternative for patients with severe mitral valve regurgitation who are considered at high risk for conventional surgical options. The early clinical experience with TMVR has shown that pre-procedural planning with computed tomography (CT) is needed to mitigate the risk of potentially lethal procedural complications such as left ventricular outflow tract (LVOT) obstruction. The goal of this review is to provide an overview of key concepts relating to TMVR pre-procedural planning, with particular emphasis on imaging-based methods for predicting TMVR-related LVOT obstruction. RECENT FINDINGS: Risk of LVOT obstruction can be assessed with CT-based pre-procedural planning by using virtual device simulations to estimate the residual 'neo-LVOT' cross-sectional area which remains after device implantation. A neo-LVOT area of less than 2 cm2 is currently thought to increase the risk of obstruction; however, additional studies are needed to further validate this cutoff value. Three-dimensional printing and personalized computational simulations are also emerging as valuable tools which may offer insights not readily confered by conventional two-dimensional image analysis. The simulated neo-LVOT should be routinely assessed on pre-procedural CT when evaluating anatomical suitability for TMVR.

Impact of simulated MitraClip on forward flow obstruction in the setting of mitral leaflet tethering: An in vitro investigation.

OBJECTIVES: We aimed to evaluate diastolic leaflet tethering as a factor that may cause mitral stenosis (MS) after simulated MitraClip implantation, using an in vitro left heart simulator. BACKGROUND: Leaflet tethering commonly seen in functional mitral regurgitation may be a significant factor affecting the severity of MS after MitraClip implantation. METHODS: A left heart simulator with excised ovine mitral valves (N = 6), and custom edge-to-edge clip devices (GTclip) was used to mimic implantation of MitraClip in a variety of positions. Anterior mitral leaflet (AML) tethering severity was varied for each case (leaflet excursion of 75°, 60°, and 45°, consistent with mild, moderate and severe tethering), and the baseline mitral annular area (MAA) was varied across samples (3.6-4.8 cm2 ). The resulting mitral valve area (MVA), and peak/mean mitral valve gradient (MVG) were measured in each case. RESULTS: AML tethering severity was a highly significant factor increasing MVG and decreasing MVA (P < 0.001). When GTclip placement was simulated with severe AML tethering, mean MVG >5 mmHg resulted more frequently than with GTclip placement alone (46% vs. 4%, respectively). However, severe AML tethering alone significantly reduced baseline MVA to 3.6 ± 0.2 cm2 , and increased baseline MVG to 3.0 ± 0.4 mmHg. At MAA above 4.7 cm2 , severe AML tethering did not cause moderate MS, even with placement of two GTclips (95% confidence). CONCLUSIONS: Our results show that diastolic AML tethering may predispose to MS after clip placement, however, MS was not observed when baseline MVA was above 4.0 cm2 . Severity of AML tethering may be an important criterion in selecting patients for edge-to-edge repair.

Left ventricular access point determination for a coaxial approach to the mitral annular landing zone in transcatheter mitral valve replacement.

INTRODUCTION: To facilitate coaxial device deployment in transcatheter mitral valve replacement (TMVR), a coaxial approach to the mitral annular plane is needed. We sought to establish a method to determine an 'orthogonal' left ventricular (LV) access point for transapical TMVR and to quantitatively characterize its location in patients with severe mitral regurgitation using cardiac computed tomography. METHODS: Cardiac CT data sets of 54 patients with moderate-severe mitral regurgitation evaluated for potential TMVR were analyzed. The D-shaped mitral annular contour was segmented and a 2-dimensional annular plane was derived, allowing for subsequent definition of the perpendicularly oriented mitral annular trajectory. The 'orthogonal' LV access point was defined as the transection point of mitral trajectory with the LV epicardial surface. The location of the access point was quantified by its epicardial distance from the true apex and by the rotational offset from a 3-chamber view. RESULTS: LV access points orthogonal to the mitral annular plane were most frequently located in the anterolateral (n = 22, 40.7%) and anterior (n = 16, 29.6%), less frequently anteroseptal (n = 6, 11.1%) and inferolateral (n = 5, 9.3%) ventricular segment; none inferior or inferoseptal. The mean distance to the LV apex was 17.6 ± 7.7 mm. The mean forward rotational offset from the 3-chamber view was 96.4 ± 43.4°, relating to a mean forward rotational offset of 6.4 ± 43.4° in regard to a hypothetical, secondary 90° x-plane view. No significant difference between patients with degenerative mitral valve disease or functional mitral regurgitation was observed. CONCLUSION: The location of the LV access point that provides an orthogonal trajectory to the mitral annular plane exhibits relevant inter-individual variability. It is commonly not identical with the true apex, and frequently localized in the anterolateral or anterior ventricular segments.

The quest for load-independent left ventricular chamber properties: exploring the normalized pressure-volume loop.

Left ventricular (LV) pressure-volume (P-V) loop analysis is the gold standard for chamber function assessment. To advance beyond traditional P-V and pressure phase plane (dP/dt-P) analysis in the quest for novel load-independent chamber properties, we introduce the normalized P-V loop. High-fidelity LV pressure and volume data (161 P-V loops) from 13 normal control subjects were analyzed. Normalized LV pressure (PN) was defined by 0 ≤ P(t) ≤ 1. Normalized LV volume (VN) was defined as VN=V(t)/Vdiastasis, since the LV volume at diastasis (Vdiastasis) is the in-vivo equilibrium volume relative to which the LV volume oscillates. Plotting PN versus VN for each cardiac cycle generates normalized P-V loops. LV volume at the peak LV ejection rate and at the peak LV filling rate (peak -dV/dt and peak +dV/dt, respectively) were determined for conventional and normalized loops. VN at peak +dV/dt was inscribed at 64 ± 5% of normalized equilibrium (diastatic) volume with an inter-subject variation of 8%, and had a reduced intra-subject (beat-to-beat) variation compared to conventional P-V loops (9% vs. 13%, respectively; P < 0.005), thereby demonstrating load-independent attributes. In contrast, VN at peak -dV/dt was inscribed at 81 ± 9% with an inter-subject variation of 11%, and had no significant change in intra-subject (beat-to-beat) variation compared to conventional P-V loops (17% vs. 17%, respectively; P = 0.56), therefore failing to demonstrate load-independent tendencies. Thus, the normalized P-V loop advances the quest for load-independent LV chamber properties. VN at the peak LV filling rate (≈sarcomere length at the peak sarcomere lengthening rate) manifests load-independent properties. This novel method may help to elucidate and quantify new attributes of cardiac and cellular function. It merits further application in additional human and animal physiologic and pathophysiologic datasets.